Erythromycin

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 response is shown . These effects are discussed in the view of the part that discrete DNA lesions could take in the explanation of the mechanism of toxicity of the organomercurial.

J Infect, 1983 Sep, 7(2), 111 - 7
Erythromycin compared with a combination of ampicillin and amoxycillin as initial therapy for adults with pneumonia including Legionnaires' disease; Macfarlane JT et al.; In a double blind trial erythromycin was compared with a combination of ampicillin and amoxycillin for treating adults admitted to hospital with primary pneumonia . The clinical course of 42 patients treated with ampicillin and amoxycillin was similar to that of the 49 in the erythromycin group . Fall in temperature, symptomatic recovery and radiographic improvement were similar (two-thirds made an uncomplicated recovery) . Infusion-related phlebitis was more common with erythromycin . Otherwise adverse reactions were unusual . The outcome was related principally to the cause of the pneumonia with bacteraemic/antigenaemic pneumococcal pneumonia, Legionnaires' disease, other bacterial pneumonias and psittacosis having a poor prognosis . Both forms of antibiotic therapy gave similar results but we suggest that a combination of erythromycin with ampicillin may be logical initial treatment for severe pneumonia of unknown cause.

Postgrad Med J, 1983 Aug, 59(694), 514 - 5
Transient, selective factor X deficiency and acute liver failure following chest infection treated with erythromycin BP; Hosker JP et al.; A 57-year-old man developed symptoms of a respiratory tract infection which was treated with erythromycin BP . He subsequently went into acute liver failure . Investigation of a very prolonged prothrombin time revealed a marked, selective factor X deficiency (1% of normal activity) . He later recovered virtually normal liver function and completely normal factor X activity.

Sex Transm Dis, 1983 Jul-Sep, 10(3), 151 - 2
Persistent nongonococcal urethritis associated with a minocycline-resistant strain of Ureaplasma urealyticum: a case report; Magalhaes M; Culture of urethral specimens from a 21-year-old man with nongonococcal urethritis yielded both Chlamydia trachomatis and a minocycline-resistant strain of Ureaplasma urealyticum . In such situations, the causal agent of the urethritis is frequently considered to be C . trachomatis . However, the etiology of this case was more probably linked to U . urealyticum . This conclusion emerged after observation of the following events: (1) the patient was not cured by a standard course of minocycline, despite the elimination of the chlamydiae; and (2) clinical recovery was achieved by treatment with a different drug (erythromycin), to which the ureaplasmas were susceptible and by which they were eradicated.

Sex Transm Dis, 1983 Jul-Sep, 10(3), 130 - 4
Comparison of rosaramicin and erythromycin stearate for treatment of cervical infection with Chlamydia trachomatis; Robson HG et al.; The macrolide antibiotic rosaramicin inhibits in vitro growth of Chlamydia trachomatis . Rosaramicin (1 g daily given to 18 patients for seven days) and erythromycin stearate (2 g daily given to 19 patients for seven days) were compared in the treatment of chlamydial cervicitis . Cultures of cervical specimens obtained nine to 11 days and 24-32 days after commencement of therapy were negative for all rosaramicin-treated patients seen at follow-up . The first follow-up culture of one erythromycin recipient was positive . The extent of cervicitis decreased in all patients after treatment, but the only patients to achieve a completely normal cervical appearance were those with minimal-to-moderate lesions before treatment . Gastrointestinal side effects, including nausea, vomiting, and abdominal pain, occurred in ten of 19 patients given erythromycin and in 13 of 18 given rosaramicin . Minimally elevated levels of alanine aminotransferase in serum occurred in four (22.2%) of 18 rosaramicin recipients . It is concluded that rosaramicin and erythromycin stearate both eradicate C . trachomatis cervical infection but frequently cause adverse gastrointestinal effects.

J Allergy Clin Immunol, 1983 Jul, 72(1), 34 - 9
Inhibition of methylprednisolone elimination in the presence of erythromycin therapy; LaForce CF et al.; Methylprednisolone elimination is reduced in the presence of treatment with troleandomycin (TAO), a macrolide antibiotic . To assess whether a similar interaction occurs with a more commonly used and less hepatotoxic macrolide antibiotic, erythromycin, we evaluated methylprednisolone pharmacokinetics before and after a 1 wk course of erythromycin base in nine adolescent patients with chronic asthma . These data were compared to results of studies of the troleandomycin methylprednisolone interaction evaluated in 10 adolescent asthmatic patients . Methylprednisolone clearance and apparent volume of distribution were significantly decreased and mean residence time and half-life significantly increased in the presence of both erythromycin and troleandomycin . The latter caused greater inhibition of methylprednisolone elimination . A nonlinear pattern of methylprednisolone disposition was observed in the presence of concomitant macrolide antibiotic administration . Addition of erythromycin base to methylprednisolone therapy results in inhibition of methylprednisolone elimination and may potentially increase the beneficial and adverse effects of this corticosteroid.

Ann Intern Med, 1983 Jul, 99(1), 22 - 6
Treatment of the early manifestations of Lyme disease; Steere AC et al.; During 1980 and 1981, we compared antibiotic regimens in 108 adult patients with early Lyme disease . Erythema chronicum migrans and its associated symptoms resolved faster in penicillin- or tetracycline-treated patients than in those given erythromycin (mean duration, 5.4 and 5.7 versus 9.2 days, F = 3.38, p less than 0.05) . None of 39 patients given tetracycline developed major late complications (meningoencephalitis, myocarditis, or recurrent attacks of arthritis) compared with 3 of 40 penicillin-treated patients and 4 of 29 given erythromycin (chi square with 2 degrees of freedom = 5.33, p = 0.07) . In 1982, all 49 adult patients were given tetracycline; again, none of them developed major complications . However, with all three antibiotic agents nearly half of the patients had minor late symptoms such as headache, musculoskeletal pain, and lethargy . These complications correlated significantly with the initial severity of illness . For patients with early Lyme disease, tetracycline appears to be the most effective drug, then penicillin, and finally erythromycin.

Drug Metab Dispos, 1983 Jul-Aug, 11(4), 355 - 60
Absorption of aerosolized drugs from the rat lung; Brown RA Jr et al.; To investigate the absorption of aerosolized drugs from the rat lung, anesthetized animals were allowed to inhale through a tracheal cannula liquid aerosols of drug solutions generated with an air-jet nebulizer . The aerosols had a mass median aerodynamic diameter of 2.81 +/- 0.08 micron and a geometric standard deviation of 2.53 +/- 0.05 . At various times after aerosol inhalation, the lungs were removed and assayed for the amount of compound that had not been absorbed . The times (min) necessary for 50% absorption were: antipyrine, 0.25; salicylic acid, 0.67; barbital, 0.93; amitrole, 1.3; urea, 1.4; procainamide, 2.3; guanidine, 3.1; erythromycin, 6.3; benzylpenicillin, 20.5; p-aminohippuric acid, 21.7; mannitol, 26.5; and N-acetylprocainamide ethobromide, 34.5 . Comparison with previously reported absorption rates measured after intratracheal injection of 0.1 ml of drug solution showed that drug inhaled as an aerosol was absorbed roughly two times more rapidly than when administered by intratracheal injection . The results suggest that drug absorption may be more rapid from the alveolar region than from the tracheobronchial region of the lung.

Br Med J (Clin Res Ed), 1983 Jun 18, 286(6382), 1954 - 5
Erythromycin estolate and jaundice; Inman WH et al.; Using prescription-event monitoring to determine whether erythromycin estolate was a more frequent cause of jaundice than erythromycin stearate or tetracycline 12 208 patients, for whom 5343 doctors had prescribed one of the three drugs, were identified by the Prescription Pricing Authority . Of the questionnaires sent to general practitioners about the possible occurrence of jaundice, 76% were returned . There were 16 reports of jaundice, of which four were attributable to gall stones, three to cancer, six to viral hepatitis, and only three were possibly related to an antibiotic . All three patients, in whom the antibiotic was a possible cause, had been treated with erythromycin stearate . No case was attributable to the estolate which had previously been suspected of being a more frequent cause of jaundice . Although the incidence is unknown, it is very unlikely to be more than one in 100.

Dtsch Med Wochenschr, 1983 Jun 10, 108(23), 896 - 901
{Gonorrheal urethritis--frequently a mixed Chlamydia and Mycoplasma infection . Results in 143 male patients with acute gonorrhea}; Jahn G et al.; Chlamydia trachomatis, Ureaplasma urealyticum and Mycoplasma hominis are frequently demonstrated in cases of acute gonorrhoeic urethritis . Among 143 males (average age 22.5 years) Chlamydia was demonstrated in 29%, U . urealyticum in 34% and M . hominis in 13% . Penicillin treatment of gonorrhoea does not affect Chlamydia and Mycoplasma so that these organisms will persist in the lower urogenital tract . Generally postgonorrhoeic urethritis is associated with Chlamydia or Mycoplasma infection . Nearly all patients were cured by tetracyclin or erythromycin administration . Incidence and complications of gonorrhoea co-infected with Chlamydia and Mycoplasma should be taken into account in its diagnosis and treatment.

Cutis, 1983 Jun, 31(6), 678 - 82
Topical therapy for perioral dermatitis; Bikowski JB; Six patients with perioral dermatitis were successfully treated with a combination of 1.5 percent erythromycin topical solution twice a day and topically applied hydrocortisone valerate cream . Application of erythromycin solution seems to be an effective topical therapy . Hydrocortisone valerate cream, when used in a controlled, tapered regimen seems to prevent acute rebound flare of perioral dermatitis from previous high-potency steroid use or abuse.

Arch Intern Med, 1983 Jun, 143(6), 1263 - 5
Hearing loss and erythromycin pharmacokinetics in a patient receiving hemodialysis; Kroboth PD et al.; A left upper lobe pneumonia developed in a patient who was receiving hemodialysis; he was treated intravenously with 1 g of erythromycin lactobionate every six hours . After five doses, hearing loss was noted; this was later documented by audiogram . Erythromycin serum concentrations as high as 100 mg/L and a half-life more than three times longer than normal were observed . To our knowledge, this represents the first report of reversible hearing loss associated with elevated serum erythromycin concentrations and prolonged serum half-life.

South Med J, 1983 Jun, 76(6), 714 - 8
Effect of erythromycin stearate on serum theophylline concentration in patients with chronic obstructive lung disease; Stults BM et al.; The effect of erythromycin stearate (ES) on serum theophylline concentration (STC) was studied in 15 male adult subjects taking maintenance oral theophylline for clinically stable chronic obstructive lung disease . Steady-state trough STCs were measured before and after two- and seven-day courses of ES, 500 mg every six hours . For the group as a whole, there was no significant increase in trough STC after either course of ES therapy, but five of 15 subjects exhibited increases in trough STC ranging from 4 to 8 micrograms/ml (mean increase of 5.4 micrograms/ml) within 48 to 96 hours of beginning ES therapy . Clinical theophylline toxicity developed in one of these subjects . Based on this study and others in the literature, erythromycin preparations may induce a clinically significant and potentially toxic increase in STC in a variable proportion of patients taking maintenance theophylline therapy.

Br J Vener Dis, 1983 Jun, 59(3), 196 - 7
Lymphogranuloma venereum of the rectum in a homosexual man . Case report; Mindel A; A male homosexual presented initially with bloody diarrhoea and a swelling in the left groin, which was unsuccessfully treated with erythromycin . Examination in hospital showed a rectal mass and an abscess in the left groin . Histological examination of the rectal mass and a positive lymphogranuloma complement fixation test result confirmed the diagnosis of lymphogranuloma venereum . This disease, although rare, should not be forgotten in the differential diagnosis of rectal problems in male homosexuals.

Ann Trop Med Parasitol, 1983 Jun, 77(3), 231 - 7
The blood schizontocidal action of erythromycin against Plasmodium knowlesi infections in Macaca mulatta; Warhurst DC et al.; Chloroquine-induced pigment clumping (CIPC) in vitro in Plasmodium knowlesi is inhibited by 7.3 micrograms ml-1 erythromycin . P . knowlesi infections in rhesus monkeys were controlled by doses of erythromycin which gave similar serum levels of the antibiotic . The antimalarial effect was complete but temporary, and recrudescences were noted.

J Biol Chem, 1983 May 10, 258(9), 5358 - 62
Cytochrome P-450 isozyme LM3b from rabbit liver microsomes . Induction by triacetyloleandomycin purification and characterization; Bonfils C et al.; Oral administration of triacetyloleandomycin (TAO), 1 mmol/kg/day for 7 days to mature male New Zealand White rabbit results in a significant increase in the content of liver microsomal cytochrome P-450 . This increase is accompanied by the occurrence on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the microsomes of a strong band in the zone of electrophoretic mobility associated with the LM3 isozymes and the stimulation of a number of monooxygenase activities of these microsomes including aminopyrine, chlorcyclizine, TAO, and erythromycin demethylation as well as 2-OH-estradiol and 6 beta OH-testosterone hydroxylation . Cytochrome P-450 LM3 (TAO) from these liver microsomes, purified to electrophoretic homogeneity, had Mr = 52,000 as determined by calibrated sodium dodecyl sulfate-polyacrylamide gel electrophoresis . Comparison with isozymes LM3a, LM3b, and LM3c isolated from control animals, by a number of criteria including spectral data, amino acid content, NH2-terminal sequence analysis, peptide mapping, immunological properties, and monooxygenase activities of reconstituted system, indicated that isozymes LM3 (TAO) and LM3b are very similar, if not identical, proteins . We conclude that TAO must be considered as a new type of inducer of microsomal cytochrome P-450 from rabbit liver.

Infection, 1983 May-Jun, 11(3), 161 - 3
Side-effects due to the intravenous infusion of erythromycin lactobionate; Putzi R et al.; A double-blind study was designed to test the hypothesis that local side-effects during i . v . administration of erythromycin lactobionate depend on the drug concentration and that they can therefore be minimized by dissolving erythromycin in a larger infusion volume . Forty healthy students were assigned in a randomized sequence to four 30 min infusions: 120 and 250 ml of erythromycin lactobionate (1 g in 0.9% NaCl) and 120 and 250 ml of placebo (0.9% NaCl) . An unexpectedly high incidence (95% and 80% for the infusion volumes of 120 and 250 ml, respectively) of severe systemic side-effects was observed during the first 79 infusions . Because all of these systemic side-effects were associated with the infusion of erythromycin, the study was terminated at this point . Side-effects included abdominal cramps, nausea, vomiting, dizziness and profuse sweating . The postulated positive effect of lower erythromycin concentrations in the infusion on local side-effects (pain at the infusion site, erythema) was marginal (63% vs . 45%) . Compared to the systemic side-effects, the problem of local tolerance is less important . In young adults, 30 min infusions of 1 g erythromycin lactobionate are associated with a high incidence of systemic side-effects which may be due to an age-dependent effect of the drug on smooth muscle.

Naunyn Schmiedebergs Arch Pharmacol, 1983 May, 322(4), 295 - 7
Therapeutic doses of erythromycin esteolate is not cholestatic in rats in vivo; Fiebiger I et al.; The effect of erythromycin esteolate (EE) on bile flow and bile acid secretion was studied in male Wistar rats in vivo . Daily oral treatment with a dose of up to 100 mg/kg for 1 week increased the bile flow and the bile acid secretion . Increasing the days of treatment to 4 weeks with a dose of 20 mg/kg did not alter the measured parameters significantly . Acute intravenous injection of erythromycin lactobionate (50 mg/kg) also increased bile flow and biliary bile acid secretion temporarily . The increase in bile flow may partly be due to the osmotic effect of the drug and its metabolites in bile . Since EE failed to produce cholestasis in the range of therapeutic doses, rats do not seem to be a suitable experimental model for studying EE-cholestasis.

Drug Intell Clin Pharm, 1983 May, 17(5), 370 - 2
Decrease in theophylline clearance after the administration of erythromycin to a patient with obstructive lung disease; Green JA et al.; It has been demonstrated previously that erythromycin can inhibit the total body clearance of theophylline, resulting in elevated serum theophylline concentrations . The overall incidence of this interaction and the population at risk have not been elucidated fully . Recent investigations have suggested that such an interaction is doubtful and that patients in whom this occurrence was suspect developed alterations in theophylline disposition secondary to worsening pulmonary function, not from erythromycin therapy alone . This case report shows that the interaction between theophylline and erythromycin can be clinically significant, producing as much as a 50-percent reduction in the total body clearance of the bronchodilator . The magnitude and time course of this interaction in patients with congestive heart failure and chronic obstructive pulmonary disease may differ considerably from that reported in healthy volunteers.

Biochem Pharmacol, 1983 May 1, 32(9), 1487 - 93
Formation of inactive cytochrome P-450 Fe(II)-metabolite complexes with several erythromycin derivatives but not with josamycin and midecamycin in rats; Larrey D et al.; The effects of some macrolides (4 mmoles . kg-1 p.o . daily for 4 days in vivo; 0.3 mM in vitro) on hepatic drug-metabolizing enzymes in rats were compared . One group of macrolides including previously studied compounds (oleandomycin, erythromycin and troleandomycin), as well as several other erythromycin derivatives, showed induction of microsomal enzymes and formation of inactive cytochrome P-450-metabolite complexes in vivo; this formation increased in the order: oleandomycin, erythromycin ethylsuccinate, erythromycin stearate, erythromycin itself, erythromycin propionate, erythromycin estolate and troleandomycin . Troleandomycin and, to a lesser extent, erythromycin and oleandomycin formed cytochrome P-450-metabolite complexes when incubated in vitro with 1 mM NADPH and microsomes from rats pretreated with troleandomycin or phenobarbital, but not with microsomes from control rats or rats treated with 3-methylcholanthrene . In contrast, two other macrolides, josamycin and midecamycin, showed no induction of microsomal enzymes and no detectable formation of cytochrome P-450-metabolite complexes in vivo . In vitro, these macrolides failed to form detectable complexes even with microsomes from rats pretreated with troleandomycin or phenobarbital . Hexobarbital sleeping time was unaffected by preadministration of josamycin or midecamycin (4 mmoles . kg-1 p.o.) 2 hr earlier; the in vitro activity of hexobarbital hydroxylase was not inhibited by 0.3 mM josamycin or midecamycin . We conclude that, unlike several erythromycin derivatives, josamycin and midecamycin do not form inactive cytochrome P-450-metabolite complexes in rats.

J Antimicrob Chemother, 1983 May, 11(5), 407 - 11
In-vitro sensitivity of Bordetella pertussis; Zackrisson G et al.; The in-vitro effect of ampicillin, chloramphenicol, clindamycin, erythromycin, trimethoprim and trimethoprim-sulphamethoxazole against 152 strains of Bordetella pertussis was investigated . When tested against erythromycin, 96% of the isolated strains were inhibited by less than or equal to 1 mg/l . The other antibiotics did not inhibit the growth of Bord . pertussis at concentrations judged achievable in-vivo.

Am J Med, 1983 Apr, 74(4), 609 - 14
Simultaneous infection with Legionella pneumophila and Pittsburgh pneumonia agent . Clinical features and epidemiologic implications; Muder RR et al.; Nosocomial pneumonia caused simultaneously by two organisms, Legionella pneumophila and the Pittsburgh pneumonia agent, was documented in seven patients in one institution . In all seven cases, both organisms were demonstrated by isolation from culture or visualization by direct immunofluorescence . Four patients died as a result of pneumonia, including two who received erythromycin therapy . The hospital water distribution system appeared to be the reservoir for both L . pneumophila and Pittsburgh pneumonia agent . These seven cases constituted 26.9 percent and 17.9 percent of the cases of Pittsburgh pneumonia agent and Legionnaires' disease, respectively, at one institution . Given this relatively high incidence of dual infection, it is likely that the mode of transmission for both organisms is identical . Dual infection may account for some cases of antibody response to more than one Legionella species . Historical parallels of the discovery of L . pneumophila and Pittsburgh pneumonia agent are reviewed.

Am Fam Physician, 1983 Apr, 27(4), 203 - 6
Mycoplasma pneumoniae infections; McSherry JA; Mycoplasma pneumoniae is a common pathogen . Children and young adults are at particular risk, especially if they are living in closed communities . As many as one in five persons with M . pneumoniae infection may develop pneumonia . Infection is endemic within the community, with two peaks of incidence each year . Early diagnosis requires recognition of the disease pattern, although the chest radiograph may be helpful . Tetracycline and erythromycin are effective therapy.

Clin Pharmacol Ther, 1983 Apr, 33(4), 460 - 4
Effect of erythromycin on carbamazepine kinetics; Wong YY et al.; Two recent reports of carbamazepine-induced intoxication during concurrent therapy with macrolide antibiotics prompted us to perform a carefully controlled two-way cross-over study in eight healthy male nonsmokers . Treatment A was 250 mg erythromycin every 6 hr for 5 days before and 3 days after 400 mg carbamazepine . Treatment B was 400 mg of carbamazepine alone . One half of the subjects received treatment A, then B, while the other half received treatment B, then A . There was a 4-wk washout period between treatments . Plasma samples obtained at various times up to 72 hr after the carbamazepine dose were assayed in duplicate by HPLC . The data were fit to a one-compartment open model with first-order absorption and elimination . Clearance of oral carbamazepine was lower in the presence of erythromycin (mean +/- SD, 0.290 +/- 0.074 and 0.360 +/- 0.072 1 X kg-1 X day-1) . There were no differences in apparent volume of distribution (1.01 +/- 0.20 and 1.04 +/- 0.12 1 X kg-1), elimination rate constant (0.302 +/- 0.113 and 0.348 +/- 0.079 day-1), or absorption rate constant (14.5 +/- 8.7 and 15.5 +/- 16.6 day-1) between the two treatment groups . The decrease in clearance of oral carbamazepine secondary to erythromycin indicates that further clinical studies are warranted.

J Clin Microbiol, 1983 Apr, 17(4), 631 - 5
Comparison of serological reactions of typed Fusobacterium nucleatum strains with those of isolates from humans, canines, and a Macaca mulatta monkey; Vincent JW et al.; In the present study, we compared typed F . nucleatum strains with isolates from various human periodontal diseases, canines, and a Macaca mulatta monkey . All isolates displayed biochemical reactions similar to those of the typed strains in the API 20A system (Analytab Products, Plainville, N.Y.) . The human and monkey isolates displayed both type I and type II colonial morphologies on crystal violet erythromycin agar, whereas the canine isolates displayed only type I . Antigen preparations of the human isolates, typed strains, and two of the monkey strains shared lines of identity in immunodiffusion testing . An enzyme-linked immunosorbent assay in which rabbit anti-F . nucleatum and human sera were used revealed that the human and monkey isolates, when used as antigens, allowed the detection of similar degrees of antibody activity; however, no activity was observed with the canine isolates . None of the canine isolates displayed the characteristic hemagglutination of sheep erythrocytes demonstrated by the human and monkey strains . These results suggest that F . nucleatum isolates from various human periodontal diseases share antigenic determinants . Also, differences were observed in F . nucleatum isolates from canines when compared with human and monkey strains . These findings are important when considering the immunopathological mechanisms involved in human periodontal diseases and when comparing animal model systems with naturally occurring disease in humans.

J Bacteriol, 1983 Apr, 154(1), 118 - 29
Involvement of mitochondrial protein synthesis in sporulation: effects of erythromycin on macromolecular synthesis, meiosis, and ascospore formation in Saccharomyces cerevisiae; Marmiroli N et al.; Cells of strain Z270 (MAT alpha/MAT alpha) of Saccharomyces cerevisiae did not undergo ascospore formation in buffered or unbuffered acetate sporulation medium in the presence of erythromycin . The drug inhibited sporulation when added within the first 6 to 8 h and affected to different extents some of the metabolic and sporulation-specific events that normally occur during this period . In sporulation medium, protein synthesis was highly sensitive to erythromycin, whereas RNA synthesis was unaffected and premeiotic DNA synthesis was partially inhibited . Intragenic recombination occurred at normal rates for the various heteroallelic loci tested, but rates of intergenic recombination were markedly reduced, and commitment to haploidization did not occur; hence, development was evidently arrested between intragenic and intergenic recombination . Cells kept for 8 h in acetate sporulation medium that were ready for sporulation in water without erythromycin failed to sporulate in water containing the drug, indicating that erythromycin can inhibit sporulation independent of acetate utilization.

J Hyg (Lond), 1983 Apr, 90(2), 149 - 58
Bordetella pertussis isolation in general practice: 1977-79 whooping cough epidemic in West Glamorgan; Kwantes W et al.; Some of the factors influencing the isolation rate of Bordetella pertussis during a whooping cough epidemic in West Glamorgan, Wales, are reported . The organism was isolated from 39% of patients with clinical whooping cough, pernasal swabbing being much more successful than cough plates . Isolation rates were increased in the non-immunized, particularly in the first year of life . Erythromycin and co-trimoxazole significantly reduced the isolation rate of B . pertussis but this did not occur with penicillin . In this study 20% of patients were culture positive 6 weeks after the onset of their infection . It is suggested that the Department of Health and Social Security recommendation of a minimum period of three weeks exclusion of children from school is inadequate . During the epidemic, the proportion of strains of B . pertussis containing antigen 2 more than doubled.

Nucleic Acids Res, 1983 Mar 25, 11(6), 1735 - 46
Mitochondrial circular RNAs are absent in sporulating cells of Saccharomyces cerevisiae; Schroeder R et al.; During sporulation of Saccharomyces cerevisiae the mitochondria undergo a differentiation process, leading to a "spore mitochondrion", which differs both physiologically and morphologically from vegetative cell mitochondria . We report here the behaviour of the mitochondrial transcripts during this differentiation process . The circular transcripts representing spliced introns of the two mitochondrial split genes for cytochrome b and for the subunit 1 of the cytochrome c oxidase, which are very abundant during vegetative growth, are not detectable in sporulating cells . This loss does neither take place in haploid cells under sporulation conditions nor when erythromycin is added to the medium . The process of some mRNAs is advanced in relation to their precursors in sporulating cells.

Biochem Pharmacol, 1983 Mar 15, 32(6), 1063 - 8
Effects of erythromycin on hepatic drug-metabolizing enzymes in humans; Larrey D et al.; In rats, erythromycin has been shown to induce microsomal enzymes and to promote its own transformation into a metabolite which forms an inactive complex with reduced cytochrome P-450 . To determine whether similar effects also occur in humans, we studied hepatic microsomal enzymes from six untreated patients and six patients treated with erythromycin propionate, 2 g per os daily for 7 days . In the treated patients, NADPH-cytochrome c reductase activity was increased; the total cytochrome P-450 concn was also increased but part of the total cytochrome P-450 was complexed by an erythromycin metabolite . The concn of uncomplexed (active) cytochrome P-450 was not significantly modified and the activity of hexobarbital hydroxylase remained unchanged . We also measured the clearance of antipyrine in six other patients; this clearance was not significantly decreased when measured again on the seventh day of the erythromycin propionate treatment . We conclude that the administration of erythromycin propionate induces microsomal enzymes and results in the formation of an inactive cytochrome P-450-metabolite complex in humans . However, the concn of uncomplexed (active) cytochrome P-450 and tests for in vitro and in vivo drug metabolism were not significantly modified.

Antibiotiki, 1983 Mar, 28(3), 177 - 87
{Action of erythromycin on its own producer in cultivation on broth media}; Listvinova SN et al.; The effect of erythromycin on the growth, morphogenesis and antibiotic production capacity of the organism producing it or Str . erythreus was studied . Erythromycin was added to the medium in concentrations comparable to the productivity of the organism . It was shown that at the cell level Str . erythreus was highly resistant to its own antibiotic . Still, erythromycin had a significant effect on the developmental cycle of the culture . It inhibited the growth of the mycelium capable of the antibiotic production and induced an increase in reproduction . On long-term subculturing or in the presence of erythromycin the culture showed a pronounced tendency for fragmentation similar to that in proactinomycetes, whereas under the usual conditions the mycelial growth was not disturbed . However, the structure of the septa in Str . erythreus is typical of the streptomycetes . It is concluded that Str . erythreus occupies an intermediate position between Nocardia and Streptomyces.

Antimicrob Agents Chemother, 1983 Mar, 23(3), 509 - 11
Antimycoplasmal activity of ofloxacin (DL-8280); Osada Y et al.; Ofloxacin (DL-8280; (+/-)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1- pipera-zinyl)-7-oxo-7H-pyrido{1,2,3-de}{1,4}benzoxazine-6-carboxylic acid) showed a broader spectrum and a greater potency of antimycoplasmal activity than did pipemidic acid, norfloxacin, tetracyclines, and lincomycin, but was inferior to erythromycin . Its mycoplasmacidal potency against clinical isolates of Mycoplasma pneumoniae was also greater than that of other quinolones and tetracyclines.

Medicine (Baltimore), 1983 Mar, 62(2), 120 - 8
Pneumonia due to the Pittsburgh pneumonia agent: new clinical perspective with a review of the literature; Muder RR et al.; We review the current knowledge concerning this newly recognized pathogen, Pittsburgh pneumonia agent (PPA), and present a new, comprehensive perspective of PPA based on our extensive clinical experience: 1) PPA pneumonia is more common and affects a broader range of patients than previously appreciated . 2) In the general population, the disease is not distinguishable from acute pneumonia due to other causes . Because specialized diagnostic tests are required for detection, it is likely that many cases in other hospitals go unrecognized . 3) Diagnosis is important, as erythromycin appears to improve outcome, whereas beta-lactam antibiotics and aminoglycosides, frequently used as empiric therapy for nosocomial bacterial pneumonias, do not . 4) The presence of both PPA and L . pneumophila in the same environmental sites, and the discovery of seven cases of simultaneous infection by both organisms suggest that both organisms are likely to share a common reservoir within the hospital and a common mode of transmission . 5) PPA infection occurs in a more debilitated population than does Legionnaires' disease . This may represent differences in intensity of exposure to the two organisms or may reflect inherent differences in virulence.

Cutis, 1983 Mar, 31(3), 339 - 42
Effects of treatment with erythromycin 1.5 percent topical solution or clindamycin phosphate 1.0 percent topical solution on P . acnes counts and free fatty acid levels; Puhvel SM; Twenty healthy subjects (7 men and 13 women) with average baseline P . acnes counts equal to or greater than 1.0 x 10(5) were treated twice a day for eleven days in a randomized, double-blind study with either erythromycin 1.5 percent topical solution or clindamycin phosphate 1.0 percent topical solution . P . acnes counts and free fatty acid (FFA) measurements were performed before treatment, and on Days 4 and 11 of treatment . Statistically significant reductions in P . acnes counts were produced in both groups over the course of the study . There were no statistically significant changes in FFA, free fatty acid/fatty ester (FFA/FE) ratios or triglyceride levels . With erythromycin there were greater reductions in FFA and FFA/FE ratios and greater increases in triglycerides than with the clindamycin group, but the differences between the treatment groups were not significant . No adverse reactions were reported.

Antimicrob Agents Chemother, 1983 Feb, 23(2), 201 - 6
Susceptibility of Bordetella species to growth inhibition and killing by chlorpromazine; Hewlett EL et al.; Chlorpromazine, the prototype phenothiazine tranquilizer, inhibited the growth and killed organisms of the genus Bordetella . There were striking differences, however, among the three Bordetella species . Bordetella pertussis was most susceptible, with some inhibition of growth at greater than or equal to 4 micrograms/ml and killing at 16 micrograms of chlorpromazine per ml . Bordetella parapertussis and Bordetella bronchiseptica were less susceptible, with killing at 32 and 256 micrograms/ml, respectively . Although the phenothiazines were inhibitory for Bordetella extracytoplasmic adenylate cyclase, the lethal effect occurred at a lower concentration and did not appear to involve modification of the enzyme activity . Exposure of B . pertussis to combinations of chlorpromazine and erythromycin resulted in impaired growth at concentrations lower than that of either drug alone, but there was no evidence that the two drugs interacted either synergistically or antagonistically.

Drug Intell Clin Pharm, 1983 Feb, 17(2), 105 - 9
Early reports on drug interactions; D'Arcy PF; Letters in correspondence columns or brief reports in medical journals are an essential part of an early warning system, and they are invaluable in alerting clinicians and clinical pharmacists to associations between drugs and their reactions . A survey of the literature during the first half of 1982 has identified a number of these early reports; some are purely anecdotal, others may be coincidental, but all serve to warn the practitioner of potential hazard . Brief information on the following reports of drug-drug interactions is given in this article with the intention of giving these reports wider publicity and, possibly, encouraging further observation and research to establish or disprove their validity in a larger and wider range of patients or volunteer subjects . The following interactions are reviewed: amiodarone-quinidine, lidocaine-prenylamine, erythromycin-carbamazepine, azapropazone-phenytoin, chlordiazepoxide-levodopa, gentamicin-furosemide, ethanol-aspirin, acetaminophen-coumarin anticoagulant, and cimetidine-lidocaine.

Postgrad Med, 1983 Feb, 73(2), 347, 350 - 2, 354
Legionnaires' disease . Clinical and pathologic features and current management; Francke E; "New" diseases continue to crop up . One of the most spectacular of these is Legionnaires' disease, first diagnosed after an epidemic in Philadelphia in 1976 . Analysis of stored serums, however, has shown the causative agent, Legionella pneumophila, to be the culprit in epidemics of pneumonia occurring as early as 1947 . The disease has a spectrum of presentations ranging from a self-limited syndrome of myalgias and nonproductive cough with a 24-hour incubation period to a severe pneumonia with diarrhea and delirium and up to 30% mortality . Therapy consists of erythromycin with or without rifampin . One reviewer said, "I found Dr Francke's article . . . to be an informative treatise on a fascinating subject."

Am J Med, 1983 Feb, 74(2), 281 - 8
Nosocomial Legionnaires' disease . Occurrence in recipients of bone marrow transplants; Kugler JW et al.; Nosocomial pneumonia caused by Legionella pneumophila serogroup 1 occurred in five patients after bone marrow transplantation for hematologic malignancies . Two patients died as a result of the infection despite treatment with erythromycin . Serologic screening revealed no other cases of Legionnaires' disease in 40 consecutive recipients of bone marrow transplants, giving a frequency of infection of 13 percent . These five cases represent 23 percent of the pneumonia occurring in this group of patients . Patients undergoing bone marrow transplantation are highly susceptible to infectious complications . Legionnaires' disease must now be added to the list of pathogens infecting this group of patients . Erythromycin is not generally a part of standard empiric antibiotic regimens in febrile neutropenic patients, but appears to be a reasonable addition when pneumonia does not respond to conventional, empiric treatment . Even with appropriate therapy, Legionnaires' disease remains a highly lethal infection in immunocompromised hosts.

Br J Dermatol, 1983 Feb, 108(2), 199 - 204
Benzoyl peroxide versus topical erythromycin in the treatment of acne vulgaris; Burke B et al.; In a double-blind clinical study in ninety-four subjects a 1.5% (w/v) erythromycin lotion was as effective as 5% (w/v) benzoyl peroxide gel in significantly reducing the number of small inflamed lesions and the overall acne severity . However, benzoyl peroxide also significantly reduced the number of non-inflamed lesions whereas erythromycin had no effect on these lesions . This study supports the view that, although topical erythromycin is of value in the treatment of mild or moderate acne vulgaris, long established, safe and effective remedies should not be replaced by topical antibiotics until more comparative studies and investigations on bacterial resistance have been completed.

Am Rev Respir Dis, 1983 Jan, 127(1), 121 - 5
Pneumonia and multiple lung abscesses caused by dual infection with Legionella micdadei and Legionella pneumophila; Dowling JN et al.; An immunocompromised patient developed pneumonia in which both Legionella micdadei and L . pneumophila, serogroup 6, were isolated from transtracheal aspirates in the absence of any other bacteria . Unusual features included the development of disseminated intravascular coagulation and multiple pulmonary abscesses during treatment with erythromycin, and relapse of the legionellosis after extended therapy with both erythromycin and rifampin, which was heralded by septic shock . Because simultaneous infection with two distinct species of Legionella occurs, concurrent increases in antibody titer to more than one Legionella may, in some instances, reflect multiple infection rather than cross-reacting antibody.

Chemotherapy, 1983, 29(2), 128 - 34
The pneumococcus and the mouse protection test: importance of the lag phase in vivo; Frimodt-Moller N et al.; During development of a mouse protection test with a pneumococcus type 3 we noted the importance of the immediate post-challenge lag phase of the bacteria in vivo for the effective timing of treatment with different antibiotics . The lag phase, lasting 6-8 h after intraperitoneal challenge and parallel in peritoneum and blood, was reproducible with the same and three other strains of pneumococcus type 3 . Penicillin administration during the lag phase had no effect upon survival of the mice, while a significantly improved effect was obtained after treating the mice with penicillin during the bacterial growth phase . In contrast, treatment with gentamicin or erythromycin during the bacterial lag phase was significantly more effective than administration of either drug after initiation of growth of the pneumococcus.

Pharmacology, 1983, 26(1), 40 - 5
Effects of erythromycin, aminoglycosides and doxycycline on mucociliary activity in vitro of rabbit trachea; Toremalm NG et al.; The effect of different antibiotics on the mucociliary activity of the upper respiratory tract of rabbit was tested in vitro . Erythromycin base had no effect, although erythromycin lactobionate had a minor inhibitory effect . Kanamycin and gentamicin had no inhibitory effect in high concentrations . Doxycycline had the highest mucociliary inhibitory effect; however, the toxic concentrations are more than 10 times the clinically relevant serum levels after oral administration.

Ther Drug Monit, 1983, 5(4), 405 - 7
Carbamazepine--erythromycin interaction leading to carbamazepine toxicity in four epileptic children; Hedrick R et al.; We report four cases of carbamazepine toxicity in children associated with the concurrent administration of erythromycin . They all developed clinical toxicity (ataxia, dizziness, nausea, and vomiting) when erythromycin administration was begun; symptoms disappeared after erythromycin was discontinued . Serum carbamazepine levels were measured before, during, and, in most cases, after the toxic episodes . In all cases, there was a sharp increase in carbamazepine concentration after erythromycin therapy was begun and a rapid fall once erythromycin was discontinued . Our data support the previous suggestion that erythromycin interferes with the liver microsomal metabolism of carbamazepine with a subsequent increase in blood levels of the drug.

J Int Med Res, 1983, 11(5), 285 - 8
Efficacy and tolerance of enteric-coated erythromycin base (Ery-Max) administered twice or four times daily in patients with acute bronchitis; Pekkanen PS et al.; We performed a double-blind trial of a new formulation of erythromycin base as enteric-coated pellets (Ery-Max) in the treatment of acute bronchitis in 220 patients . Subjects were randomized to receive either 500 mg twice or 250 mg four times a day for 10 days . The response to treatment as assessed clinically and by changes in sputum purulence was the same in the two groups . Thus 97% and 98% of the patients had a good or improved clinical effect . Treatment was well tolerated, but side-effects were encountered more often in the q.i.d . group (p greater than 0.05) . In conclusion, the study showed that the enteric-coated erythromycin as pellets, given twice or four times daily for 10 days, was well tolerated and equally effective in acute bronchitis . Hence, the more convenient b.i.d . regimen can be recommended.

Eur J Clin Pharmacol, 1983, 25(2), 271 - 3
Erythromycin absorption in healthy volunteers from single and multiple doses of enteric-coated pellets and tablets; Hovi T et al.; The absorption of erythromycin from two different enteric-coated preparations was evaluated in three groups of healthy volunteers . After a single dose, taken after an overnight fast, absorption was significantly better from enteric-coated pellets than from tablets; both the mean peak serum concentration and the peak mean level were higher (p less than 0.01) in all three groups, and the mean area under the serum concentration-time curve (AUC) was at least 65% larger . Eight out of 23 subjects showed no or only a very low serum concentration after the enteric-coated tablets . In a follow-up study, 250 mg doses were given 6-hourly for 3 days, and again the mean maximum serum concentration was significantly higher (p less than 0.05) after the pellets . In conclusion, enteric-coated pellets led to more regular and predictable absorption of erythromycin than did coated tablets.

Sex Transm Dis, 1983 Jan-Mar, 10(1), 36 - 8
Erythromycin failure in the treatment of syphilis in a pregnant woman; Hashisaki P et al.; A pregnant woman with a history of allergy to penicillin was diagnosed as having primary syphilis . Two successive courses of erythromycin therapy failed to cure the infection . Penicillin desensitization and therapy were initiated and were successful . The newborn was diagnosed as having probable congenital syphilis . This case emphasizes the need for close follow-up of pregnant women after erythromycin treatment for early syphilis.

South Med J, 1983 Jan, 76(1), 91 - 3
Interaction between warfarin and erythromycin; Schwartz J et al.; In the patient described, marked exacerbation of the hypoprothrombinemic response to warfarin coincided with the addition of erythromycin to the drug regimen . A subsequent study in rats provided evidence that erythromycin is capable of increasing the anticoagulant response to single doses of warfarin . On the basis of case findings, preliminary laboratory data, and related clinical data we conclude that the interaction between warfarin and erythromycin is one of potential significance.

Med Pediatr Oncol, 1983, 11(3), 180 - 1
Brief communication: Legionnaire's disease successfully treated in acute myelocytic leukemia during severe neutropenia; Guthrie TH Jr et al.; A patient with acute nonlymphocytic leukemia developed progressive lung infiltrates and unremitting fevers during a profound neutropenic state . Legionnaire's disease was diagnosed by simple immunologic studies and successfully treated with erythromycin . This index case alerts physicians toward a treatable infection which would not normally be susceptible to the empiric antibiotic regimens given neutropenic patients with fevers.

Z Erkr Atmungsorgane, 1983, 161(1), 25 - 7
{The detection of the agent of Legionnaires' disease--a confirmation of Koch's postulates}; Naumann G; The genus Legionella, belonging to the family of Legionellaceae, comprises nowadays seven species, among which Legionella pneumophila might be the most important . The identification of the agent is difficult because L . pneumophila is very pretentious requiring peculiar conditions concerning culture medium, temperature, and time . The initial cultivation will succeed the best in an atmosphere enriched with CO2 . The demonstration of serum antibodies will succeed by means of indirect immunofluorescence; recently the micro-agglutination test is vastly applied . The clinical picture of Legionellosis is characterized by an atypical pneumonia with a serious course in most cases . The Pontiac Fever is an illness with milder course than the classical form of Legionellosis . Erythromycin and Rifampicin are the chemotherapeutics of choice.

Mol Gen Genet, 1983, 190(3), 504 - 10
The role of the nuclear gene "mitochondrial mutability control" (MMC1) in the process of mutability of the mitochondrial genome by different mutagens in Saccharomyces cerevisiae; Donnini C et al.; The accumulation of respiratory deficient (RD) mutants in Saccharomyces cerevisiae depended upon the mutagens used and upon the presence of the nuclear gene previously identified as MMC1 (one) which we showed to control the spontaneous and the erythromycin-induced RD mutability . In this paper data are reported about the accumulation of RD mutants in the presence of manganous ions (Mn++) and UV which was higher in the mmc1 (one) than in MMC1 strains . We found that the characters 'low spontaneous' and 'low induced' RD mutability by erythromycin, manganous ions and UV, were controlled by the same genetic determinant . In the presence of manganous ions, also the frequency of antibiotic resistant mutants capR and eryR was higher in the mmc1 strains . Moreover, the accumulation of RD mutants in the presence of berenil, 5-fluorouracil and basic fuchsin was higher in the mmc1 than in MMC1 strains . In contrast, RD mutants accumulation by acriflavine and ethidium bromide treatments did not appear affected by the MMC1 genetic constitution.

Mol Gen Genet, 1983, 190(2), 215 - 21
Tests of the ribosome editor hypothesis . II . Relaxed (relA) and stringent (relA+) E . coli differ in rates of dissociation of peptidyl-tRNA from ribosomes; Menninger JR et al.; Derivatives of isogenic stringent (relA+) and relaxed (relA) strains of Escherichia coli were compared in respect of rates of the dissociation of peptidyl-tRNA from ribosomes during protein synthesis . The derivatives both contained a mutant pth gene which rendered temperature-sensitive their peptidyl-tRNA hydrolase (E.C . 3.1.1.29) activities . After shifting from permissive 30 degrees C to non-permissive 40 degrees C, dissociated peptidyl-tRNA accumulated and was assayed chemically or by its cytotoxic effects . In unperturbed (except for the temperature shift) cultures the relA strain accumulated peptidyl-tRNA significantly more slowly than did its relA+ isogenic cousin . Both strains responded approximately equally to non-lethal doses of erythromycin or to starvation for amino acids . Both these perturbations enhanced the dissociation and accumulation of peptidyl-tRNA . While growing at 30 degrees C, both strains responded significantly to a nutritional downshift from growth in medium containing glucose plus amino acids to growth in medium containing only amino acids . Taken together the results suggested that different intracellular concentrations of ppGpp in unperturbed cells, attributable to the different relA alleles, could account for the differences in dissociation and accumulation of peptidyl-tRNA . Our observation of a lower rate of dissociation of peptidyl-tRNA in the relA strain, coupled with the reported lower intracellular ppGpp and lower accuracy of protein synthesis, is consistent with the idea that relA strains have less efficient ribosomal editing of erroneous peptidyl-tRNA.

Microbiologica, 1983 Jan, 6(1), 9 - 18
The role of glucose and aminoacid starvation in the sensitivity of protein and RNA synthesis to cycloheximide and erythromycin in the yeast Saccharomyces cerevisiae; Tassi F et al.; In Saccharomyces cerevisiae dependence of ribonucleic acid synthesis on protein synthesis occurring during nutritional shift down conditions was evidenced . The results obtained indicated that yeast had "stringent control" of ribonucleic acid synthesis and that this control was reversed by cycloheximide only under glucose starvation or ammonia starvation in the presence of acetate as carbon source (phenotypic relaxation) . Therefore, it appeared that the "phenotypic relaxation" of RNA synthesis depended on the carbon source present in the medium suggesting that the process could be negatively controlled by glucose or by some glucose catabolite(s) . Such a phenotypic relaxation was sensitive to erythromycin treatment . On the other hand, total protein synthesis carried out during amino-acid starvation in the presence of glucose or ammonia starvation in the presence of acetate was 30%-40% inhibited by erythromycin, showing that in these conditions sensitivity to a non legitimate inhibitor could be triggered off in an haploid strain, and that such sensitivity did not depend on the presence of glucose in the medium.

Med Cutan Ibero Lat Am, 1983, 11(1), 33 - 8
{Fulminating acne}; Vasconcelos AM et al.; A 17 years old male patient with acne vulgaris since the age of 13 is reported in whom a sudden exacerbation occurred with large, inflammatory, exquisitely tender, nodular lesions on the back and shoulders . Some were ulcerated and covered by hemorrhagic crusts . The lesions healed with large, unsightly, atrophic scars . With the cutaneous flare there was fever, arthralgia, loss of weight, leucocytosis and increased ESR . Systemic antibiotics (tetracycline, dicloxacillin, erythromycin) were unable to prevent or control the general and cutaneous symptoms that rapidly subsided on oral steroids . The initial relatively low dose could not be significantly reduced without further relapses . Attempts to replace prednisone by dapsone or clofazimine were unsuccessful . The relevant literature is reviewed and commented upon.

J Int Med Res, 1983, 11(1), 38 - 41
Tolerance and efficacy of erythromycin stearate tablets versus enteric-coated erythromycin base capsules in the treatment of patients with acne vulgaris; Bleeker J; In a randomized, and for the investigator, blind study side-effects and efficacy of two oral erythromycin preparations have been compared . Twenty patients with acne vulgaris, predominantly of the face, received erythromycin stearate tablets and another twenty patients received erythromycin enteric-coated base capsules . All patients were given 500 mg twice a day for 2 weeks . An improvement was seen in both groups, most pronounced in patients treated with the stearate tablets . Twenty per cent of the patients given the base preparation withdrew from therapy due to gastro-intestinal side-effects, as compared to 10% in the erythromycin stearate group.

Mol Gen Genet, 1983, 192(3), 295 - 300
Characterisation of a mutant from Escherichia coli lacking protein L15 and localisation of protein L15 by immuno-electron microscopy; Lotti M et al.; Two mutants lacking protein L15 from the ribosome as determined by two dimensional gels were investigated using a number of different immunological methods . One strain was found to possess several protein L15 moieties which differed in net charge and in size . The other showed no evidence of L15 cross-reacting material (CRM) on the ribosome or in the supernatant . Ribosomes of this strain were used as a control in the process of the localisation of protein L15 on the surface of the large subunit of Escherichia coli ribosomes . Antigenic determinants mapped in the angle between the central protuberance and the L1 protuberance . Protein L15 has been assigned a central role in the large subunit in vitro assembly map, in peptidyltransferase activity and in the binding of erythromycin, so the significance of a mutant lacking this protein is discussed.

Biomed Pharmacother, 1983, 37(6), 298 - 300
Bromoderma caused by carbromalhydroxyzine hydrochloride; David M et al.; A patient is described who developed a pyoderma-gangrenosum-like ulcer of the leg and acneiform eruption on the face following intake of carbromalhydroxyzine hydrochloride (Dormax) . Serum levels of bromide were found to have risen to 105 mg% . There was a return to normal levels of serum bromide and regression of the skin lesions after one week of treatment with natrium chloride and erythromycin . The importance of increasing awareness of the potential hazards of bromide administration is stressed.

Lancet, 1982 Dec 18, 2(8312), 1361 - 4
Measurement of pulmonary erythromycin concentration in patients with lobar pneumonia by means of positron tomography; Wollmer P et al.; The concentration achieved in the infected tissue is of fundamental importance in the use of antibiotics . Erythromycin labelled with the positron-emitting nuclide carbon-11 and positron tomography were used to compare local concentrations of this antibiotic in the pneumonic and unaffected lungs of five patients with lobar pneumonia . The time course of uptake of erythromycin into the extravascular compartment (i.e., the intracellular, interstitial, and alveolar compartments) of the pneumonic lung was measured . The mean extravascular concentrations obtained during the first hour after an intravenous injection of 270 mg erythromycin lactobionate were similar in the pneumonic lung and the unaffected lung (5.5 +/- 2.2 and 6.6 +/- 2.2 micrograms/g, respectively) . An effective concentration of erythromycin was reached in the pneumonic lung within 10 min of the injection and was maintained throughout the period of measurement (60 min).

Fed Regist, 1982 Dec 30, 47(251), 58370 - 2
Pharmaceutical Reimbursement Board; final maximum allowable cost (MAC) determinations for certain drug products--Health Care Financing Administration . Final notice; Tinea capitis in Brooklyn; Tinea capitis, a disease of children, occurs throughout the United States . We studied 144 clinically diagnosed cases of tinea capitis within a 12-month period . Ninety-six of them had positive cultures; Trichophyton tonsurans grew in 89% and Microsporum organisms in 11% . Ninety-five (99%) of the patients with positive cultures were black, and one (1%) was hispanic . The peak incidence was in the 4-to-5-year age group . Boys and girls were equally affected . Sixty percent of the 96 culture-proved cases were noninflammatory, and 40% were inflammatory (kerions) . In four patients, the initial clinical manifestations were severe diffuse seborrhealike scales and crusting of the scalp with minimal alopecia . Mycologic and clinical cure were obtained by a mean of 4.7 weeks of griseofulvin therapy . Neither systemic erythromycin, topical antifungal agents, nor systemic prednisone resulted in earlier eradication . However, prednisone caused the inflammation of the kerions to subside dramatically.

J Bacteriol, 1982 Dec, 152(3), 1301 - 2
Genetic analysis of acrA and lir mutations of Escherichia coli; Henson JM et al.; An analysis of acrA (acriflavine- and methylene blue-sensitive) and lir (lincomycin- and erythromycin-sensitive) mutants of Escherichia coli indicated that these mutations are probably within the same gene.

J Infect Dis, 1982 Dec, 146(6), 741 - 5
Serologic diagnosis of whooping cough by an enzyme-linked immunosorbent assay using fimbrial hemagglutinin as antigen; Granstrom M et al.; Diagnosis of whooping cough by an enzyme-linked immunosorbent assay (ELISA) that measures serum IgG, IgM, and IgA antibody to the fimbrial hemagglutinin of Bordetella pertussis was compared to isolation from nasopharyngeal swabs in a prospective study . Of 77 patients with upper respiratory tract infections of unknown etiology in which B . pertussis infection could not be excluded on clinical grounds, 26 were culture-positive, including one for Bordetella parapertussis . All 26 patients were positive by ELISA except one asymptomatic erythromycin-treated patient (ELISA sensitivity, 96%) . Among culture-negative patients, 24 additional patients were positive by ELISA . Thus, only about one half of the patients with whooping cough were identified by culture under optimal conditions . Positive titers of IgM antibody and/or high titers of IgG antibody in the first serum sample, allowing for a rapid diagnosis, were found only in 26 (53%) of 49 serologically positive patients . By combining culture testing with serology, rapid diagnosis was obtained in 41 (82%) of 50 patients.

Nucleic Acids Res, 1982 Nov 11, 10(21), 6571 - 7
Identification of two erythromycin resistance mutations in the mitochondrial gene coding for the large ribosomal RNA in yeast; Sor F et al.; Two independent erythromycin resistance mutations, ER514 and ER221, have been identified in the mitochondrial gene coding for the 21S ribosomal RNA . The two mutations were found to be identical, corresponding to a A to G transition at the nucleotide position 1951 of the ribosomal RNA gene . In the secondary structure model of the ribosomal RNA, the ER resistance site is found at the proximity of the chloramphenicol resistance sites located about 500 bases downstream.

Br J Clin Pharmacol, 1982 Oct, 14(4), 495 - 9
Pharmacokinetic interaction between theophylline and erythromycin; Iliopoulou A et al.; 1 The pharmacokinetics of a single intravenous dose of theophylline alone and during the fifth day of treatment with 500 mg erythromycin every 8 h was studied in six healthy subjects . 2 At the same time the pharmacokinetics of erythromycin at steady-state on the fourth day of the treatment (alone) and the fifth day (during the theophylline co-administration) were also studied . 3 Mean +/- s.d . theophylline clearance was decreased from 62 +/- 15.4 to 53 +/- 10.3 ml min-1 (P less than 0.05) and elimination half-life rose from 7.1 +/- 1.9 to 7.7 +/- 2 h (P less than 0.05) when erythromycin was co-administered . 4 Mean +/- s.d . erythromycin area under the curves (0-8 h) and (0-oc) were reduced from 6.09 +/- 3.2 to 3.8 +/- 2.5 micrograms ml-1 h and 7.2 +/- 3.6 to 5.0 +/- 2.9 micrograms ml-1 h (P less than 0.05) in the presence of theophylline . Mean steady state and maximum steady state concentrations were also reduced from 0.75 +/- 0.4 to 0.47 +/- 0.3 microgram ml-1 (P less than 0.05) and 1.45 +/- 0.87 to 0.85 +/- 0.51 microgram ml-1 (P less than 0.05) respectively . 5 The potential clinical implications of this indication should be considered.

J Am Acad Dermatol, 1982 Oct, 7(4), 504 - 10
Erythromycin therapy in bullous pemphigoid: possible anti-inflammatory effects; Fox BJ et al.; Two patients with bullous pemphigoid treated with erythromycin demonstrated improvement . This response suggests that erythromycin may be a fairly safe supplemental drug which may allow a lower dose of systemic steroid, or may be of benefit when used alone or in combination with topical steroids in treating patients who are not ideal candidates for a systemic steroid . Erythromycin appears to have a significant anti-inflammatory effect, and possible mechanisms for this effect are proposed . One of the patients was a 4 1/2-year-old girl whose disease manifested several unusual features, making diagnosis difficult . A brief summary of differential immunofluorescent findings in childhood bullous diseases is also presented.

Nouv Presse Med, 1982 Sep 18, 11(36), 2699 - 702
{Legionnaires' disease with digestive tract lesions . One case}; Fogliani J et al.; In the case reported pulmonary Legionella infection was diagnosed by sputum cultures even though immunofluorescence tests were negative . The patient had positive Coomb's test due to circulating auto-antibodies which disappeared after he recovered . The course of the disease was prolonged by perforation of the coecum requiring excision of the colon and terminal ileostomy . Erythromycin had to be given intravenously . Pathological examination of the digestive tract lesions showed inflammatory colitis with presence of Legionella pneumophilia which seemed to have been responsible for the complication . This is the first time a digestive lesion caused by this organism is described, adding yet another extrapulmonary visceral involvement to those already reported and suggesting that Legionella may spread throughout the body.

J Gen Microbiol, 1982 Sep, 128 (Pt 9), 2011 - 5
Transient repression of erythromycin formation in Streptomyces erythraeus; Escalante L et al.; The effect of a D-glucose on growth and erythromycin production by Streptomyces erythraeus was investigated . D-Glucose stimulated growth and caused a strong but temporary suppression of antibiotic formation . Maximum specific suppression of erythromycin formation occurred at a carbohydrate concentration of 20 mg ml-1 . A non-metabolizable analogue of glucose, 2-deoxy-D-glucose, also suppressed antibiotic formation . Since glucose caused a decrease in erythromycin formation only when added before the stage of antibiotic production, we conclude that this sugar exerted a transient repressive effect on erythromycin biosynthesis.

Chest, 1982 Sep, 82(3), 382 - 4
Legionnaires' disease . Association with severe bronchospasm and hypoventilation; Rosenberg DM et al.; A 31-year-old man with legionnaires' disease, who presented with severe pneumonia and hypoxemia, later developed severe bronchospasm and marked hypercapnia, a complication not previously reported in Legionella infection . He responded to therapy with erythromycin and a bronchodilator.

Am J Dis Child, 1982 Sep, 136(9), 817 - 21
Oral v topical erythromycin therapies for chlamydial conjunctivitis; Patamasucon P et al.; Results of oral and topical erythromycin therapy in 41 infants under 4 months of age with chlamydial conjunctivitis were evaluated in randomized clinical trial . After three weeks of treatment, relapse or reinfection of the eye occurred in four of 19 patients (21%) in the topical therapy group and in three of 22 patients (13.6%) in the oral therapy group (p less than .69) . In the topical therapy group, chlamydiae were isolated from nasopharyngeal cultures of eight patients (42%) during or after therapy . Chlamydiae were eradicated from the nasopharynx of the six colonized patients treated with oral erythromycin . All relapses responded to a course of oral erythromycin therapy . We conclude that both modes of therapy are comparable for treatment of chlamydial conjunctivitis, but that oral therapy has the advantage of eradicating nasopharyngeal colonization.

Clin Pediatr (Phila), 1982 Sep, 21(9), 545 - 50
Prophylaxis of neonatal conjunctivitis . An analytic review; Bernstein GA et al.; The recommendation by the Centers for Disease Control (CDC) that erythromycin and tetracycline ointments, as well as silver nitrate solution, are acceptable regimens for prophylaxis of gonococcal ophthalmia neonatorum (GON) has resulted in widespread local review of policies for ocular prophylaxis . The data concerning the efficacy and side effects of these agents are somewhat confusing or nonexistent . We discuss the etiologies of neonatal conjunctivitis and the topical and systemic agents used for prophylaxis of GON . We also review all studies that have compared the efficacy of one prophylactic agent with that of another agent or with no prophylaxis . It is found that all three agents have similar efficacy in preventing GON, although silver nitrate has been used more extensively in populations at high risk for GON . However, since Chlamydia trachomatis is the most common infectious cause of neonatal conjunctivitis in the United States at this time, and erythromycin appears to be very effective in prevention of neonatal conjunctivitis due to C . trachomatis, it may have an advantage over the other two agents . In addition, erythromycin use is associated with fewer ocular reactions than is silver nitrate.

Clin Pharmacokinet, 1982 Sep-Oct, 7(5), 401 - 20
Circadian changes of drug disposition in man; Reinberg A et al.; Circadian (approximately equal to 24 hours) and other endogenous biological rhythms, detectable at all levels of organisation, constitute a temporal structure in all animal species, including man . Circadian, circannual, and other rhythmic changes in biological susceptibility and response of organisms to a large variety of physical and chemical agents, including medications and foods, are rather common phenomena . A better understanding of periodic and thus predictable changes in drug effects can be attained through consideration of three complementary concepts: the chronopharmacokinetics of a drug (rhythmic changes in its pharmacokinetics), the chronesthesy (rhythmic changes in susceptibility of target biosystems to the drug), and the chronergy (the drug-integrated overall effects) . The chronopharmacokinetics of many drugs have been evaluated in man including sodium salicylate, aspirin, indomethacin, paracetamol (acetaminophen), phenacetin, amidopyrine, theophylline, digitalis, propranolol, clorazepate, hexobarbitone (hexobarbital), lithium, phenytoin (diphenylhydantoin), nortriptyline, ethanol, erythromycin, ampicillin, sulfasymazine, sulphanilamide, cisplatin (cis-diammine dichloroplatinum), d-xylose, ferrous sulphate, potassium chloride, hydrocortisone and prednisolone, among others . The roles presumably played by circadian rhythms in drug metabolising liver enzymes and kidney function are summarized, and the practical implications of chronopharmacokinetics, aiming both to improve in a quantitative manner the metabolic fate of a drug and its effectiveness, are discussed.

Proc Natl Acad Sci U S A, 1982 Sep, 79(18), 5602 - 6
Erythromycin resistance due to a mutation in a ribosomal RNA operon of Escherichia coli; Sigmund CD et al.; There are seven ribosomal RNA operons (rrn operons) in Escherichia coli . A single rrn operon was amplified by use of a multicopy recombinant plasmid containing a complete rrnH operon . rrnH thereby has the potential to contribute a greater fraction of the rRNA found in ribosomes . Erythromycin-resistant mutants were isolated from cells containing the plasmid, and at least one mutation to resistance was shown to reside in rrnH on the plasmid . Erythromycin resistance was retained when a major deletion was introduced into the 16S rRNA gene and was abolished by deletions that affect the 16S and 23S rRNA genes but do not alter the 5S rRNA gene or non-rrnH DNA . Cell-free S30 protein-synthesizing extracts from cells containing the mutant plasmid have an increased resistance to erythromycin . The selection procedure used to isolate erythromycin-resistance mutations in rrnH may allow, with minor modifications, the isolation of mutations in rrn operons that change resistance of the ribosome to other antibiotics or that alter other properties of ribosomes.

Dig Dis Sci, 1982 Aug, 27(8), 701 - 4
Hepatotoxicity to both erythromycin estolate and erythromycin ethylsuccinate; Keeffe EB et al.; Two patients experienced hepatotoxicity associated with erythromycin estolate (Ilosone) usage, followed 13 and 15 years later by an hepatotoxic reaction with administration of erythromycin ethylsuccinate (E.E.S.) . These cases provide further evidence for erythromycin ethylsuccinate-associated hepatotoxicity and demonstrate erythromycin cross-sensitivity after previous erythromycin estolate liver injury . Hepatotoxicity to both sensitivity after previous erythromycin estolate liver injury . Hepatotoxicity to both estolate and ethylsuccinate preparations of erythromycin stimulates speculation regarding the potentially hepatotoxic moiety of the erythromycin molecule . Furthermore, these cases suggest that all erythromycin preparations should be avoided or used only with careful monitoring in patients with previous erythromycin-associated liver injury.

Sex Transm Dis, 1982 Jul-Sep, 9(3), 128 - 31
Treatment of chlamydial urethritis in men and Chlamydia trachomatis-positive female partners: comparison of erythromycin and tetracycline in treatment courses of one week; Scheibel JH et al.; Seventy-one consecutive men who had Chlamydia trachomatis-positive nongonococcal urethritis were assigned randomly to treatment for one week with either tetracycline or erythromycin (1g daily) . Seventy men completed the study . At follow-up, there were two therapeutic failures among 36 patients treated with erythromycin, and two failures among 34 patients treated with tetracycline . Twenty-four C . trachomatis-positive female contacts were randomly assigned to treatment regimens similar to those of the men . There was one treatment failure among 12 women treated with erythromycin, and no failure among 12 treated with tetracycline . In this study the urethral smears contained fewer than five leukocytes per high-power field in 16% of the C . trachomatis-positive men with symptoms suggestive of urethritis.

J Clin Pharmacol, 1982 Jul, 22(7), 321 - 5
Pharmacokinetics of erythromycin in normal and alcoholic liver disease subjects; Hall KW et al.; The objective of this study was to compare the pharmacokinetic behavior of erythromycin in normal volunteers with that in subjects with alcoholic liver disease . Six normal volunteers received 500 mg erythromycin as an intravenous infusion or as two 250-mg enteric-coated tablets in a crossover fashion . The pharmacokinetics of erythromycin after intravenous administration was best described as a two-compartment model . The elimination half-life was 1.6 +/- 0.7 hours (mean +/- S.D.) after the intravenous dose and 2.0 +/- 0.7 hours after the oral dose . In patients with alcoholic liver disease the elimination half-life after oral administration of two 250-mg enteric-coated tablets was 3.2 +/- 0.5 hours, significantly different from that in normal subjects, probably due to impaired metabolism . The difference in half-life does not require dosage adjustment in this patient population . The systemic availability of erythromycin was 33.5 per cent (range 10.5 to 79.3 per cent).

Arch Dermatol, 1982 Jul, 118(7), 474 - 7
Enhanced percutaneous penetration with 1-dodecylazacycloheptan-2-one; Stoughton RB; 1-Dodecylazacycloheptan-2-one (Azone) is a new agent that enhances the percutaneous absorption of a number of different chemicals . This report delineates the enhancement of penetration of clindamycin phosphate, erythromycin base, fusidate sodium, fluorouracil, desonide, amcinonide, and triamcinolone acetonide . For this purpose 1-dodecylazacycloheptan-2-one can be used in concentrations as low as 1% . It is colorless, relatively odorless, nontoxic, and can be applied neat to human skin without any irritation.

Am Rev Respir Dis, 1982 Jun, 125(6), 759 - 61
Concurrent legionnaires' disease and active pulmonary tuberculosis; Milder JE et al.; A 68-yr-old man was admitted to the hospital with severe Legionnaires' disease, which was serologically confirmed by a 6-fold increase in antibody titers to Legionella pneumophila, serogroup 1 . The patient improved dramatically with intravenously administered erythromycin therapy but was discharged from the hospital with residual debility and pulmonary complaints later recognized as being caused by active pulmonary tuberculosis . The diagnostic and therapeutic confusion engendered by the concurrence of these pulmonary infections is discussed.

Can Med Assoc J, 1982 Jun 1, 126(11), 1295 - 1300
Q fever in maritime Canada; Marrie TJ et al.; Only nine cases of Q fever were recorded in Canada in the 20 years prior to 1978 . In the 18 months from August 1979 to January 1981 the disease was diagnosed serologically in six patients from the Maritime provinces . All were epidemiologically unrelated and none had been exposed to animals . Five had pneumonia and one had chronic Q fever with probable prosthetic valve endocarditis . Three of the five pneumonia patients presented with signs and symptoms of an acute lower respiratory tract infection and were indistinguishable clinically from other patients with atypical pneumonias . The other two with pneumonia presented with nonresolving pulmonary infiltrates and complained of decreased energy . Four of the five pneumonia patients responded well to treatment with erythromycin; the fifth required two courses of tetracycline . The patient with chronic Q fever had a large amount of cryoglobulins in his serum and evidence of immune complex disease . These cases indicate that Q fever should be considered as a possible cause of atypical pneumonia in Canada.

Cutis, 1982 Jun, 29(6), 624 - 5, 628-32
Comparison of topical erythromycin 1.5 percent solution versus topical clindamycin phosphate 1.0 percent solution in the treatment of acne vulgaris; Thomas DR et al.; Commercial topical solutions of erythromycin 1.5 percent and clindamycin phosphate 1.0 percent were evaluated in a randomized, double-blind, twelve-week comparison in sixty-six patients with moderate acne . Both treatment groups showed significant reductions of total lesions, inflammatory lesions, and papules . Additionally, the group using erythromycin 1.5 percent showed significant decreases in total noninflammatory lesions and closed comedones, and the group using clindamycin phosphate 1.0 percent showed significant reductions in pustules . The only statistically significant differences between the treatments were the greater reductions in closed comedones for those patients using erythromycin 1.5 percent and greater reductions in pustules for those patients using clindamycin 1.0 percent . Nearly two thirds of the patients in each group had a good or excellent overall response after twelve weeks . One erythromycin-treated patient discontinued treatment because his wife became sensitized to it . This reportedly also occurred with the use of topical clindamycin . Other side effects were minor or transient . In this study, topical erythromycin 1.5 percent and clindamycin 1.0 percent appeared to be clinically equivalent for treating moderate facial acne.

Clin Pharmacol Ther, 1982 May, 31(5), 579 - 86
Theophylline kinetics and ventilatory flow in bronchial asthma and chronic airflow obstruction: influence of erythromycin; Richer C et al.; The kinetics and the effects on the ventilatory function peak expiratory flow rate (PEFR) of a single 600-mg oral dose of theophylline were investigated in 46 adult patients with bronchial asthma (BA) and in 16 adult patients with chronic airflow obstruction (CAO) . In the former, theophylline induced an early and potent bronchodilatation (60% rise in PEFR), the kinetics of which correlated with plasma concentration . Theophylline was also effective in patients with CAO, but the magnitude of its bronchodilator effect was less than in those with BA: this was despite plasma concentrations of much the same order . In adult patients with BA (but not with CAO) theophylline plasma levels and bioavailability are higher after simultaneous erythromycin dosing.

Chest, 1982 May, 81(5), 563 - 5
The effect of erythromycin on theophylline pharmacokinetics at steady state; Maddux MS et al.; We compared steady-state theophylline pharmacokinetics in 13 healthy adults before and immediately after erythromycin therapy . All subjects received a five-day course of oral aminophylline 3 mg/kg every six hours prior to and during a five-day course of oral erythromycin stearate (1 g daily) . Each subject acted as his own control . Multiple serum samples were collected over ten hours following the last dose of aminophylline during both the control and experimental phases of the study . Erythromycin did not significantly affect theophylline clearance (P greater than 0.70), elimination (P greater than 0.75), or volume of distribution (P greater than 0.30) . We found no evidence of a pharmacokinetic interaction between theophylline and erythromycin at steady state . Worsening pulmonary function may be responsible for altered theophylline pharmacokinetics in patients coincidentally receiving erythromycin.

Antimicrob Agents Chemother, 1982 May, 21(5), 811 - 8
Erythromycin, carbomycin, and spiramycin inhibit protein synthesis by stimulating the dissociation of peptidyl-tRNA from ribosomes; Menninger JR et al.; In mutant Escherichia coli with temperature-sensitive peptidyl-tRNA hydrolase (aminoacyl-tRNA hydrolase; EC 3.1.1.29), peptidyl-tRNA accumulates at the nonpermissive temperature (40 degrees C), and the cells die . These consequences of high temperature were enhanced if the cells were first treated with erythromycin, carbomycin, or spiramycin at doses sufficient to inhibit protein synthesis in wild-type cells but not sufficient to kill either mutant or wild-type cells at the permissive temperature (30 degrees C) . Since peptidyl-tRNA hydrolase in he mutant cells is inactivated rapidly and irreversibly at 40 degrees C, the enhanced accumulation of peptidyl-tRNA and killing were the result of enhanced dissociation, stimulated by the antibiotics, of peptidyl-tRNA from ribosomes . The implications of these findings for inhibition of cell growth and protein synthesis are discussed . Certain alternative interpretations are shown to be inconsistent with the relevant data . Previous conflicting observations on the effects of macrolide antibiotics are explained in terms of our observations . We conclude that erythromycin, carbomycin, and spiramycin (and probably all macrolides) have as a primary mechanism of action the stimulation of dissociation of peptidyl-tRNA from ribosomes, probably during translocation.

Arch Sci Med (Torino), 1982 Apr-Jun, 139(2), 247 - 50
{Salbutamol combined with erythromycin and sobrerol in the therapy of pertussis}; Crosca V et al.; The results of treatment carried out with salbutamol, erythromycin and fluidifiers in 20 children with whooping cough are reported . Results in all cases were much superior to those that have been obtained up to the present with the use of antibiotics alone or associated with hyperimmune gammaglobulins and/or sedatives . A speedier and more complete resolution of symptomatology was observed in the group where treatment was instituted earlier.

Med Lett Drugs Ther, 1982 Mar 19, 24(605), 29 - 34
Treatment of sexually transmitted diseases; Erythromycin binding to human serum; Erythromycin binding to human serum was measured under conditions of binding equilibrium . The binding is sensitive to pH changes, decreasing at acid pH . Over a great range of serum dilution, the bound fraction is semilogarithmically related to serum concentration . Binding is shown to be completely reversible . With increasing erythromycin concentration a specific part of binding is saturable and specifically displaceable by erythromycin is specifically bound to a single class of noninteracting binding sites with an apparent dissociation constant Kd = 5.9 microM (38 degrees C) . The kinetic and thermodynamic parameters at 25 degrees are: Kd = 8.4 microM, delta H degrees = +4.4 X 10(3) cal per mole, delta G degrees = 6.9 X 10(3) cal per mole, delta S degrees = +38 e.u.

J Clin Pharmacol, 1982 Feb-Mar, 22(2-3), 125 - 30
The effects of erythromycin on theophylline elimination in normal males; May DC et al.; The effects of three erythromycin preparations on theophylline elimination kinetics were examined in 23 male subjects . Subjects received 6 mg/kg of the theophylline elixir orally and elimination kinetics were determined . The population was then randomized to receive either a lactose placebo, erythromycin base, erythromycin stearate, or erythromycin ethylsuccinate . Each 250-mg preparation was given four times a day for six days . On day seven, a repeat kinetic study was performed . The mean theophylline half-life of controls was 7.8 +/- 2.6 hours . The half-life increased significantly in all erythromycin treatment groups . The increase for the base, stearate, and ethylsuccinate groups was 51.7, 21.3, and 60.3 per cent, respectively . The total body theophylline clearance decreased significantly in all treatment groups . This was not associated with biochemical evidence of hepatitis . Three of four smokers who received erythromycin manifested no increase in theophylline half-life, in contrast to one of 13 nonsmokers . There was no difference in the percentage theophylline bound to serum protein for any of the erythromycin treatment groups or controls as determined by ultracentrifugation.

Ann Intern Med, 1982 Feb, 96(2), 173 - 5
Hemodialysis fistula infections caused by Legionella pneumophila; Kalweit WH et al.; Legionella pneumophila was found in the infected hemodialysis fistulas of two patients . The first patient developed an infection of the fistula during acute illness with Legionnaires' pneumonia . Legionella organisms were shown to be present in the graft by direct immunofluorescent staining . The second patient developed an infection of the hemodialysis fistula 3 weeks after completing a course of erythromycin therapy for Legionnaires' pneumonia . Legionella organisms were found by direct immunofluorescence in purulent material that was obtained from the graft, and serogroup 1 L . pneumophila was isolated from the pus . The frequency with which the organism causes infection of hemodialysis access sites is unknown . Increased awareness by physicians that L . pneumophila produces extrapulmonary disease may result in more frequent detection of these infections.

Pathol Biol (Paris), 1982 Feb, 30(2), 102 - 5
{A case of pulmonary mycobacteriosis due to Mycobacterium intracellulare (author's transl)}; Demoulin L et al.; An M . intracellulare, rough strain (serotype 7) has been isolated from sputum of a sixty-year old patients . This patient was a political prisoner in Germany between 1942-1945 and had contracted pulmonary tuberculosis with the cavity in the upper lobe of the right lung . A strain of mycobacterium susceptible to antituberculous drugs was isolated from his sputum in 1973 . Since 1979, the isolation of M . Intracellulare has been accompanied by clinical signs of pulmonary mycobacteriosis, i.e . persistence of the cavity in spite of antituberculous treatments reapparition of cough with sputum, general weakness . Intradermo-reaction with specific sensitin gives a strong positive reaction, contrasting with a weak reaction with PPD tuberculin . As the antibiogram of the strain shows a susceptibility to cotrimoxazole and erythromycin, the patient underwent a therapy with the combination sulfamethaxozale-trimethoprime and erythromycin, for 4 months . At the end of this treatment, he seems to have recovered completely . The radiological aspect of the lungs remains unchanged . Although the source of contamination remains unknown, one thinks on the basis of bibliographica data, that it can be found in human beings, or seldom in animals (a pig, a bird) or in nature (a pond).

J Pharm Sci, 1982 Feb, 71(2), 161 - 6
Analysis of oral suspensions containing sulfonamides in combination with erythromycin ethylsuccinate; Elrod L Jr et al.; The sulfonamides and erythromycin ethylsuccinate in combination oral suspensions were determined by high-performance liquid chromatography and automated turbidimetry, respectively . The chromatographic procedure was rapid, specific, and stability-indicating for sulfisoxazole acetyl and the trisulfapyrimidines using a reversed-phase system with UV detection at 254 nm . Erythromycin ethylsuccinate did not interfere with the sulfonamide analysis and these compounds were assayed with relative standard deviations (RDS) ranging from +/- 2.1 to +/- 3.1% . Erythromycin ethylsuccinate was determined as erythromycin with RSD values of +/- 1.3 or 3.5% without interference by the sulfonamides present.

J Am Dent Assoc, 1982 Feb, 104(2), 181 - 4
Dental treatment and management of a patient with a prosthetic heart valve; Baumgartner JC et al.; The American Heart Association committee recognizes that their regimens do not cover all situations . Each patient should be evaluated individually . The necessity for parenteral therapy or oral erythromycin to continue for 48 hours after all dental procedures should be reevaluated on a case-by-case basis . On the other hand, if the dental manipulation involves an infected site, perhaps antibiotic therapy should be continued until signs of the inflammation subside . Dentists and physicians must use their clinical judgement in prescribing antibiotics . However, as Kaye proposed, any deviation in prescribing antibiotics should be in the direction of higher doses or more effective antibiotics . In addition, practitioners must provide adequate patient education and follow-up . Unfortunately, a negligent dentist, a physician giving poor or inadequate advice, or a patient not following instructions may turn a simple dental procedure into a life-threatening situation and potential tragedy.

Biochem Pharmacol, 1982 Feb 1, 31(3), 359 - 65
The binding characteristics of some adrenergic beta-receptor antagonists to human serum proteins; Lemaire M et al.; Binding of pindolol and 8 related compounds was studied in vitro by equilibrium dialysis . The overall binding in serum was compared with the binding to the main, isolated, serum proteins . Most substances show both saturable and non-saturable binding in serum . The saturable and main binding is to alpha 1-AGP, the low non-saturable binding corresponds to albumin and lipoprotein binding . The binding to alpha 1-AGP is characterized by approximately one binding site and association constants K ranging from 10(4) to 10(6) M-1 . The binding of pindolol to alpha 1-AGP is strongly inhibited by propranolol, lidocaine, erythromycin, imipramine and TBEP . Significant correlations were found between log NK and log partition coefficient octanol-phosphate buffer suggesting that the protein binding of the 9 adrenergic beta-receptor antagonists to all serum proteins, including alpha 1-AGP, is predominantly hydrophobic in nature.

Dtsch Med Wochenschr, 1982 Jan 22, 107(3), 92 - 6
{Severe forms of mycoplasma pneumonia (author's transl)}; Hennemann HH et al.; Respiratory tract infections with mycoplasma can cause severe infiltrating pneumonia (with pleuritis), associated with marked inflammatory reactions (maximal E.S.R., high leucocytosis with shift to the left and marked alpha 2-proteinaemia) . Serial measurements of cold-agglutinin titres as well as complement-fixation reaction to Mycoplasma pneumoniae will confirm the diagnosis . Atypical forms of pneumonia can also be documented in that they respond only to erythromycin and extrapulmonary complications accompany the disease, giving them a protean character . In two such patients there was the clinical picture of pneumonia with high fever and marked inflammatory reaction, associated with anicteric hepatitis . In one there was also thoracic lymphadenitis, myositis and rash, in the other a meta- and post-infectious polyarthritis.

Z Hautkr, 1982 Jan 15, 57(2), 69 - 77
{Local acne therapy with erythromycin}; Schmidt JB et al.; Results of treatment of papulo-pustular acne vulgaris with erythromycin in a topical preparation . Demonstration of changes in the bacterial spectrum in acne lesions during therapy . Erythromycin could not be detected in the serum even after extensive application.

J Biol Chem, 1982 Jan 10, 257(1), 389 - 94
Massive accumulation of phosphatidic acid in conditionally lethal CDP-diglyceride synthetase mutants and cytidine auxotrophs of Escherichia coli; Ganong BR et al.; Escherichia coli mutants partially defective in CTP: phosphatidic acid cytidylyltransferase (CDP-diglyceride synthetase) are more resistant to the antibiotic erythromycin than are isogenic wild type strains . When 100 micrograms/ml erythromycin is added to nutrient agar plates, it is possible to obtain a 30-fold enrichment for cds mutants from a mutagen-treated stock, as judged by colony autoradiography (Ganong, B . R., Leonard, J . M., and Raetz, C . R . H . (1980) J . Biol . Chem . 255, 1623-1629) . Using this approach, we have isolated 38 new cds mutants, nine of which are unable to grow at a culture pH greater than 8 . A typical conditionally lethal mutant like GN80 contains a 3 to 5% phosphatidic acid below pH 7 . Above pH 8, GN80 accumulates phosphatidic acid to about 30% of the total membrane lipid, while the de novo syntheses of phosphatidylethanolamine and phosphatidylglycerol are abruptly inhibited by over 10-fold . GN80 loses viability after 60 min at pH 8.5, and the liponucleotide pool of GN80 is about one-seventh that of an isogenic wild type, GN85, under these conditions . The pH optimum of the residual CDP-diglyceride synthetase present in extracts of GN80 is 0.5 pH units lower than normal . Twenty-one of 26 spontaneous pH-resistant revertants of GN80 concomitantly regain parental levels of the enzyme . Our results constitute definitive physiological proof that CDP-diglyceride is an obligatory precursor for over 90% of the phosphatidylethanolamine and phosphatidylglycerol in E . coli . Independent evidence for this is provided by the observation that cytidine auxotrophs, which are defective in the conversion of UTP to CTP, also accumulate very high levels of phosphatidic acid after 1 h of cytidine starvation.

Eur J Clin Pharmacol, 1982, 23(5), 435 - 40
Should erythromycin dose be altered in haemodialysis patients?
Iliopoulou A, Downey K, Chaput de Saintonge DM, Turner P.
Erythromycin kinetics were studied in 17 patients with end stage renal failure treated with maintenance haemodialysis and 9 normal volunteers to discover if dialysis patients needed a modified dose . The elimination half life in dialysis patients (on dialysis days) was similar to that reported in normal subjects . Only small amounts of drug appeared in the dialysate, no patient loosing more than 9 mg in one dialysis . Both patients and volunteers had similar plasma concentrations 8 h after the end of a 5-day course . Protein-binding did not change significantly during dialysis and was similar to that reported in normal subjects . We conclude that dialysis patients requiring 1.5 g of erythromycin stearate daily or less can be given normal doses.

Vet Med Nauki, 1982, 19(1), 97 - 103
{Blood concentrations and anti-Borrelia anserina activity of erythromycin salts in birds}; Stoianova-Zaikova L et al.; Tested was comparatively the antispirochaetal activity of erythromycin asparaginate (EA), thiocyanate (ET), and lactate (EL) in a total of 314 chickens, pullets and cockerels artificially infected with Borrelia anserina (strains Surnevo and Pamoukchii) . The antibiotics were applied via the crop, with the drinking water, and subcutaneously . The general status of the birds mortality rate, spirocheataemia, and the blood level of antibiotics were followed up along with the effect of EA and ET on the post vaccinal immunity against spirochaetosis . The crop application of EA, ET, and EL at rates of 25000 and 50000 IU/kg from the day of infection for 3 days produced a good prophylactic effect (with single birds only there was transient spirochaetaemia without death cases) . At 15000 UI/kg the prophylactic effect was very weak . EA, ET, EL at 120, 180, 250, and 300 IU/kg with the drinking water, and at 150000 and 350000 UI/kg with the feed in the course of 3 to 7 days from the day of infection did not have satisfactory antispirochaetal effect because the birds did not readily accept the medicated water and feed . A comparatively better antispirochaetal effect was established with EA and ET . These antibiotics were found not to inhibit the conference of post vaccinal immunity . Highest blood levels and longest retention were by EA . Very good results were obtained with the subcutaneous application of EA at 25000, 18000, and 15000 IU/kg, once daily in the course of 3 days from the day of infection.

Infection, 1982, 10 Suppl 2, S99 - 101
{The pharmacokinetics of 1,000 mg erythromycin lactobionate i . v . in patients with respiratory tract infections (author's transl)}; Sietzen W; Pharmacokinetic data were determined in 16 patients with respiratory tract infections who had received 1,000 mg erythromycin lactobionate i . v . The infusion lasted 60 or 30 minutes . The peak concentrations were 33.3 mg/l (60 min group) and 34.4 mg/l (30 min group) . The elimination half-lives were 2.0 h and 1.9 h . The concentrations are considerably higher than those found following the peroral administration of erythromycin . We did not find a cumulative effect after four administrations at 12-hour intervals . The clinical efficacy was good.

Infection, 1982, 10 Suppl 2, S84 - 5
Erythromycin (2 X 1 g) as a Regimen for community-acquired pneumonia; Simmen HP et al.; Erythromycin is regarded more and more as the primary therapy for community-acquired pneumonia . In a prospective study, treatment with erythromycin was evaluated in cases of community-acquired pneumonia requiring hospitalisation . Therapy was started intravenously with 1 g erythromycin lactobionate b . i . d., followed by 1 g erythromycin ethylsuccinate b . i . d., administered orally, until the patient had definitely recovered . Twenty-four patients with documented pneumonia were admitted to the study; five were excluded since the infections were caused by bacteria which were not susceptible to erythromycin . Nineteen patients responded well to therapy . No severe side-effects could be observed . Erythromycin (1 g b . i . d.) appears to be an effective, well-tolerated regimen for severe community-acquired pneumonia.

Infection, 1982, 10 Suppl 2, S113 - 5
{The binding of erythromycin to proteins in the serum of humans during various infections (author's transl)}; Barre J et al.; A large amount of the erythromycin in the serum is bound to acidic alpha 1-glycoprotein; the exact share is dependent on the concentration . The concentration of acidic alpha 1-glycoprotein can be elevated during infections . Thus, a larger amount of the erythromycin is bound, leaving less free antibiotic.

Infection, 1982, 10 Suppl 2, S102 - 4
The penetration of erythromycin into the middle ear; Sundberg L et al.; The penetration of erythromycin was studied in 108 cases of secretory otitis media . Erythromycin ethylsuccinate was given orally in a dosage of 30-60 mg/kg/day and samples of middle ear effusion were obtained at different intervals . The concentration of erythromycin in the middle ear effusions reached the plasma level (1.1-1.2 mg/l) after 26 hours . The plateau levels were maintained during the steady state . Elimination was slow; 14 hours after the last dose of a ten-day treatment, the concentration of erythromycin in the middle ear effusions was still as high as 0.9 mg/l, compared to 0.2 mg/l in plasma . The concentration of erythromycin in the middle ear effusions surpassed the MICs of most respiratory pathogens . Erythromycin can thus be regarded as a suitable drug in the treatment of otitis media . Furthermore, since the respiratory mucosa reacts in a uniform manner to an inflammatory stimulus, the result of this penetration study is valid for inflammatory diseases in any area lined with respiratory epithelium.

Mol Gen Genet, 1982, 185(3), 418 - 23
Antimutators of mitochondrial and nuclear DNA in Saccharomyces cerevisiae . Relationship with gamma-ray sensitivity; Bianchi L et al.; In Saccharomyces cerevisiae ten antimutator mutants have been isolated . The spontaneous occurrence of mitochondrial mutants resistant to erythromycin, oligomycin, and diuron is decreased 2-60-fold in these strains . The rate of forward and reverse spontaneous mutations of the nuclear genome is also reduced . The meiotic progenies arising from the crosses of seven mutants (LB1, LB2, LB4, LB5, LB6, LB7, LB10) with an isogenic parental strain exhibit 2 : 2 segregations and therefore are the result of mutations in a single nuclear gene . The six mutants LB1, LB2, LB4, LB6, LB7, LB10 are semidominant and determine six complementation groups . The mutant LB5 is dominant and therefore cannot be assigned to any complementation group . The mutants, LB1, LB4 and LB10 are gamma-ray sensitive and, by tetrad analysis, it has been shown that gamma-ray sensitivity and spontaneous antimutability are the result of a single nuclear gene mutation . The other three mutants LB3, LB8, and LB9 exhibit complex tetrad segregations, typical of cytoplasmic inheritance and do not complement each other . However, although the mutations are semidominant, it has not been possible to detect any antimutator cytoductant among some 500 cytoductants carrying the karl-1 nucleus . These results suggest that either several nuclear genes are involved in the expression of the antimutator phenotype or that the antimutator gene is located on nonchromosomal elements of the nucleus . The present study leads to the conclusion that a large number of nuclear genes are able to control simultaneously the spontaneous mutation rate of nuclear and mitochondrial genes . Since out of the ten antimutator mutants, three are also deficient in the repair of gamma-ray damage, it is also concluded that spontaneous and gamma-ray-induced lesions of DNA can be repaired by the same error-free process.

Infection, 1982, 10 Suppl 2, S105 - 7
The penetration of erythromycin into Waldeyer's ring--tonsil and adenoid tissue; Sundberg L et al.; Erythromycin ethylsuccinate was given orally (30-60 mg/kg/day) to 72 otherwise healthy children for different intervals before adenoidectomy . The concentration of erythromycin was assessed in homogenized tissue, in whole blood and in plasma, making it possible to calculate blood-free tissue levels . The tissue levels (1.5-2.0 mg/l) were the same as the plasma levels . Six patients with chronic tonsillitis were given 1000 mg erythromycin ethylsuccinate via a gastric tube, and tonsillectomy a froid was performed three to five hours later . This unusual mode of administration was chosen to avoid tonsil surface contamination, which might cause artificially high values . The concentration of erythromycin was assessed as described above . The levels of erythromycin in the tonsil tissue were the same as the concomitant plasma levels . Erythromycin has been shown to penetrate into adenoid and tonsil tissue and to attain levels similar to the simultaneous plasma levels . It may be inferred from this study that erythromycin penetrates into other lymphatic localities to the same degree.

Curr Med Res Opin, 1982, 8(2), 67 - 74
Evaluation of the clinical efficacy of erythromycin, amoxicillin and co-trimoxazole in the treatment of acute respiratory tract infections in paediatric patients; Bottone E et al.; An open comparative study was carried out in 56 paediatric patients with acute upper and lower respiratory tract infections to assess the efficacy and tolerance of treatment with erythromycin, amoxicillin or co-trimoxazole . Patients were treated with the standard recommended doses for 7 to 10 days . Diagnoses included otitis, tonsillitis, pharyngitis, epiglottiditis, pertussis, scarlet fever and bronchitis and, when possible, pathogens were isolated and identified at the initial visit . The clinical findings showed that all three treatment resulted in statistically significant decreases in final mean values for temperature, pulse rate and respiration rate . Twenty of the patients with positive cultures on entry became negative by the end of treatment . No clinical side-effects, were reported with any of the treatments . Overall assessment of response and acceptability of treatment by physician and patient/parent indicated that erythromycin was at least equally as effective as the other two drugs in treating common respiratory diseases found in paediatric practice.

Scand J Infect Dis Suppl, 1982, 32, 111 - 5
Chlamydial eye infection in adults; Ronnerstam R et al.; In Western industrialized countries, conjunctivitis caused by Chlamydia trachomatis is most prevalent in adults at about the age of 20 years . In the case of classical trachoma in developing countries, the highest incidence of active disease occurs in children between 2 and 5 years of age . Inclusion conjunctivitis in adults is usually an autoinfection, resulting from a concomitant genital chlamydial infection . By contrast, in endemic trachoma the infection is spread from eye to eye . Only rarely has a nongenital transmission of inclusion conjunctivitis been inferred, among medical personnel and after swimming-pool bathing . Neonates with inclusion blennorrhea also may transmit the infection to family members . Diagnosis relies on the demonstration of C . trachomatis recovered from infected eyes . Treating chlamydial eye infection in adults means controlling the concomitant genital infection as well . The recommended treatment is oral tetracycline or erythromycin.

Mol Gen Genet, 1982, 186(2), 204 - 16
Translational attenuation of ermC: a deletion analysis; Hahn J et al.; ermC is a plasmid gene which specifies resistance to macrolide-lincosamide-streptogramin B antibiotics . The product of ermC was previously shown to be an inducible rRNA methylase, which is regulated translationally, and a mechanism for this regulation, termed the translational attenuation model, has been proposed . This model postulates that alternative inactive and active conformational states of the ermC mRNA are modulated by erythromycin-induced ribosome-stalling during translation of a leader peptide . In the present study the translational attenuation model was tested by constructing a series of deletants missing the ermC promoter and portions of the regulatory (leading) region . In these mutants, ermC transcription is dependent on fusion to an upstream promoter . Depending on the terminus of each deletion within the regulatory region, determined by DNA sequencing, ermC expression is observed to be either high level and inducible (like the wild-type), high level and noninducible, or low level and noninducible . The translational attenuation model predicts that as the deletions extend deeper into the leader region, successively masking and unmasking sequences required for translation of the methylase, an alternation of high and low level methylase expression will be observed . These predictions are confirmed . Based on this and other information, the model is refined and extended, and both direct translational activation and kinetic trapping of a metastable active intermediate during transcription are proposed to explain basal synthesis of methylase and to rationalize the effects of certain regulatory mutants.

Helv Paediatr Acta, 1982, 37(1), 83 - 8
Acute sinusitis in children - results of different therapeutic regimens; Helin I et al.; The clinical material consisted of 92 children aged 1-15 years with symptoms and signs of acute sinusitis, roentgenologically verified . Sixty-one were treated with penicillin-V, 16 with pivampicillin, and 15 with erythromycin . Decongesting therapy was given to all . Altogether 77 (83.7%) were cured by a single 10-day course of treatment . The initial success rate did not vary with the type of antibiotic used . Children treated with penicillin-V had, however, a high relapse rate with H . influenzae . Because of growth of H . influenzae, 15 patients required 2 or 3 courses of treatment . The study shows that acute sinusitis in children is usually an uncomplicated disease . Almost all children will improve during a single 10-day course of treatment with antibiotics and decongestants provided that the antibiotic chosen is one to which H . influenzae is susceptible . It is therefore stressed that if penicillin-V is used as the drug of choice in acute sinusitis, the dose must be large enough to eradicate H . influenzae . As judged from this study, adenoidectomy and intranasal antrostomy are rarely indicated.

Mol Gen Genet, 1982, 188(2), 256 - 60
Genetics of mitochondrial ribosomes of yeast: mitochondrial lethality of a double mutant carrying two mutations of the 21S ribosomal RNA gene; Julou C et al.; Among the mitochondrial conditional mutations localized in the gene coding for the 21S ribosomal RNA, one--ts 902--produces severely reduced amounts of 21S RNA and 50S subunit . We investigated its physiological properties and found that this thermosensitive mutation was associated with highly pleiotropic effects . The mutant phenotype is associated with cell death in certain conditions, and with a massive accumulation of rho- mutants at non-permissive temperature . Furthermore, interactions with the sites of action of erythromycin and chloramphenicol, both localized within the 21S rRNA, were detected . The mutant is hypersensitive to erythromycin and has a cis-incompatibility with the chloramphenicol-resistant mutation CR321 . Ts 902 thus appears to have a dual effect, not only at the ribosomal level but also at a cellular level.

Med Cutan Ibero Lat Am, 1982, 10(3), 151 - 8
{A new salt of erythromycin (A-137 or erythromycin lauryl sulfate) in the topical treatment of acne}; Perez Lopez M et al.; Thirty six patients affected of acne vulgaris, preferently inflammatory, graded from I to IV according to Plewig & Kligman scale, were included in a double blind trial of erythromycin laurilsulfate (A-137) alcoholic solution versus only the vehicle, both for topical . The solutions were assigned after randomisation and both groups were found to be statistically comparable in what concerned to age, sex and length of the disease and initial number of the different lesions . The treatment has been carried over 8 weeks, the solution was applied 3 times daily and controls were made fortnightly . It was assessed: a) Individual count of lesions existing in one side of the face; b) Grade of severity (I to IV); c) Frontal and lateral colour pictures; d) Overall opinion of patient . The statistical analysis of results shows significant differences between both groups in behalf of A-137 in the following parameters: number of closed comedones in the 2nd week (P less than 0,05), in closed comedones (P less than 0,05) and pustules (P less than 0,005) during the 4th week, in the number of pustules (P less than 0,025) during the 6th week and in closed comedones (P less than 0,05), papules (P less than 0,05) and pustules (P less than 0,0,25) at the end of the 8 weeks treatment . The severity grade was equally lower (P less than 0,025) in the A-137 group on the 8th week . There were no intolerance phenomena reported nor any kind of unwanted side effects during the study.

Acta Derm Venereol, 1982, 62(5), 454 - 6
Demodex folliculorum hominis (Simon): incidence in a normomaterial and in patients under systemic treatment with erythromycin or glucocorticoid; Boge-Rasmussen T et al.; A study was made of 20 cilia and sebum from 20 nasal follicles from each of 86 persons . In a normomaterial aged 20-30 years . Demodex folliculorum was present in the nasal follicles in 25% and in the cilia in 29% of the subjects . This is consistent with the very high incidence we found 10 years ago . Systemic erythromycin treatment did not erradicate the mite, but the incidence decreased in both regions . Systemic glucocorticoid treatment lowered the incidence in the nasal region, whereas the incidence increased in the ciliary region.

Biochim Biophys Acta, 1981 Dec 18, 678(3), 300 - 15
Biosynthesis of vitamin B-12 . Part I . Role of the ribosomal proteins in vitamin B-12 biosynthesis; Pezacka E et al.; 1 . 70 S ribosomes isolated from strains of Escherichia coli 113-3, K12 and B take part in vitamin B-12 biosynthesis from AdoCbi-GDP, NAD and dimethylbenzimidazole in the presence of enzymes of the cytosol fraction . 2 . 70 S ribosomes from E.coli 113-3 bind Ado{58Co}Cbi-GDP . This reaction is independent of fusidic acid . 3 . Proteins from 5 S RNA complex as well as l3 protein isolated from E.coli 113-3 ribosomes catalyze vitamin B-12 biosynthesis . The main catalytic function in this reaction is preformed by protein L18 . 4 . Vitamin B-12 biosynthesis proceeding in the presence of isolated ribosomal proteins is inhibited by fusidic acid, chloramphenicol and vernamycin but not by erythromycin . 5 . Vitamin B-12 synthesized in the presence of isolated ribosomal proteins is biologically active.

Tubercle, 1981 Dec, 62(4), 277 - 9
Injection abscesses due to mycobacterium chelonei occurring in a diabetic patient; Jackson PG et al.; The case of a young fit diabetic patient who suffered from injection abscesses is presented . Mycobacterium Chelonei var chelonei was the organism responsible . The organism was difficult to isolate, but skin tests yielded valuable results . The abscesses responded to treatment with erythromycin and cotrimoxazole.

J Allergy Clin Immunol, 1981 Dec, 68(6), 427 - 31
Effect of erythromycin on theophylline kinetics; Prince RA et al.; The effect of erythromycin base on theophylline kinetics was studied in eight informed, nonsmoking, adult males who received a 15-min infusion of theophylline (aminophylline) 5 mg/kg, prior to (control) and after (experimental) a 7-day course of 1 gm daily erythromycin base (E-Mycin) . Each subject acted as his own control . Multiple serum samples were collected for 24 hr after each dose and were analyzed for theophylline by high-pressure liquid chromatography . The mean +/- SD pharmacokinetic parameters for each phase of study were as follows: apparent volume of distribution (L/kg) 0.45 +/- 0.05 (control), 0.41 +/- 0.05 (experimental); clearance (ml . min/kg) 0.83 +/- 0.17 (control), 0.60 +/- 0.11 (experimental); elimination half-life (hr) 6.65 +/- 1.88 (control), 8.10 +/- 1.58 (experimental) . Erythromycin significantly affected the elimination half-life and clearance of theophylline (p less than 0.05) . The apparent volume of distribution was unaffected (p greater than 0.05) . Therefore patients being administered theophylline appear to be at added risk for the development of toxicity when erythromycin is added to the therapeutic regimen.

Cutis, 1981 Dec, 28(6), 596, 599 - 600, 606 passim
Human chlamydial infections; McCormack WM et al.; Chlamydiae are obligate intracellular parasites, bacteria with a peculiar biology . They belong to the genus Chlamydia which includes two species: C . psittaci and C . trachomatis . A wide range of hosts, including birds, mammals and man can be infected by chlamydiae . The diseases chlamydiae can produce include psittacosis, lymphogranuloma venereum, trachoma, inclusion conjunctivitis, urethritis, cervicitis, pelvic inflammatory disease, and neonatal pneumonia . The diagnosis of chlamydial infection may be made by visualization of the organism in direct smears, isolation of the agent in cell culture, or by demonstrating a significant rise in antibody titer . Chlamydial infection may be treated with tetracycline, erythromycin, or sulfonamides.

J Toxicol Sci, 1981 Nov, 6(4), 271 - 86
Studies on nitrosamine formation by the interaction between drugs and nitrite . II . Hepatotoxicity by the simultaneous administration of several drugs and nitrite; Kawanishi T et al.; The alterations of biochemical parameters, namely, glutamic oxaloacetic transaminase and glutamic pyruvic transaminase in serum, hepatic microsomal drug oxidation systems, glucose-6-phosphate dehydrogenase and lysozomal enzymes in hepatic soluble fraction were investigated for the purpose of semiquantitatively estimating the hepatotoxicity caused by the interaction of several drugs and sodium nitrite in rats . The simultaneous administration of aminopyrine and sodium nitrite induced the alterations of these parameters . However, these alterations were not induced by the administration of antipyrine and sodium nitrite . Therefore the alterations were thought to be mainly due to N-nitrosodimethylamine formed . The administration of 0.4 mmole/kg of aminopyrine and 1.0 mmole/kg of sodium nitrite was thought to induce the alterations to almost the same extent as induced by 0.15 mmole/kg of N-nitrosodimethylamine . The simultaneous administrations of sodium nitrite and several other drugs with tertiary amino groups, namely oxytetracycline, diphenhydramine, oleandomycin, erythromycin and minocycline induced small alterations of these parameters . However, these alterations were not thought to relate to the hepatic injury induced by N-nitrosodimethylamine . Therefore the amount of N-nitrosodimethylamine formed from these drugs in rats was thought to be rather small . We also investigated the effect of several antioxidants on the alterations of biochemical parameters induced by aminopyrine and sodium nitrite . Ascorbic acid, sodium erythorbate and propyl gallate inhibited these alterations . On the other hand, sorbic acid did not.

In Vitro, 1981 Nov, 17(11), 979 - 84
Growth inhibition and morphologic modulation of human fibroblastlike cells by erythromycin; Martinez AO et al.; In vitro exposures of mass cultures and clones of human diploid fibroblastlike cells to erythromycin, in concentrations of 50 to 400 micrograms/ml, results in increasing degrees of growth inhibition and augmented cell volume, with a shift toward larger proportions of cells of the epithelioid type and fewer of the fibroblast type . These alterations were reversed upon subculture in the absence of the antibiotic.

Int J Clin Pharmacol Ther Toxicol, 1981 Nov, 19(11), 494 - 7
The pharmacokinetics of two erythromycin esters in plasma and in saliva following oral administration in humans; Ducci M et al.; An improved highly sensitive fluorimetric methods has been employed to measure plasma and saliva levels of erythromycin propionate and stearate in eight healthy volunteers following a single oral dose of 7.5 mg/kg . The plasma curves exhibited a mean half-life of 5.22 +/- s . e . m., 0.86 h-1 for the propionate and 2.97 +/- 0.22 h-1 for the stearate . Peak levels were reached at the 2nd h (4.07 +/- 0.29 microgram/ml for the propionate; 2.15 +/- 0.14 microgram/ml for the stearate) . The area under the total plasma concentration curve was about 3-fold higher in the case of propionate . The concentration in saliva was about 20% of the corresponding concentration in plasma for the propionate and about 25% for the stearate . A significant positive correlation was observed between plasma and saliva levels for both macrolides.

Sex Transm Dis, 1981 Oct-Dec, 8(4 suppl), 321 - 5
Treatment of syphilis: a short critical review; Panconesi E et al.; Four decades of treatment of syphilis with penicillin confirm the absolute superiority of this drug in all stages of the disease . Various long-acting repository preparations (particularly benzathine penicillin G) are used in treatment of early and late syphilis, and even for prophylactic treatment, with satisfactory results . Treatment schedules and follow-up criteria for examination and indications for retreatment vary little among various authors and countries . Adverse reactions to penicillin, in particular the allergic reactions, make alternative treatment with other antibiotics (tetracyclines, erythromycin, etc) sometimes necessary.

Br Med J (Clin Res Ed), 1981 Sep 12, 283(6293), 696 - 7
Whooping cough in adults; Trollfors B et al.; During the 1970s whooping cough returned in Sweden after an absence of more than 10 years and is now seen in all age groups, During a three-year period 174 adults with culture-verified whooping cough were identified in Gothenburg . Most of the patients had typical symptoms with whooping attacks and often vomiting . The disease was long lasting but complications were rare . Physicians should be aware that whooping cough may occur in adults, since adults may be an important source of infection for infants and erythromycin given in the catarrhal phase may modify the clinical course.

Klin Monatsbl Augenheilkd, 1981 Sep, 179(3), 149 - 56
{Chlamydial disease of the eye: a report on 27 cases . Clinical picture, differential diagnosis, treatment (author's transl)}; Sundmacher R et al.; During the past five years a presumptive diagnosis of ocular chlamydial disease has been made in 90 patients consulting the outpatient department of Freiburg University Eye Clinic . The diagnosis was confirmed by different methods (giemsa stains, chlamydia cultures and serology, electron microscopy and histology) in 27 cases . The clinical spectrum included inclusion blennorrhea in newborns as well as inclusion conjunctivitis, TRIC keratoconjunctivitis and sporadic trachoma in adults . Presumably the incidence of the disease is much higher than indicated by our figures . We suspect a very high number of undiagnosed cases . These patients usually do not receive proper therapy (tetracyclin or erythromycin for at least three weeks) and their disease may run a protracted course with the risk of permanent eye damage.

Arch Dermatol, 1981 Sep, 117(9), 551 - 3
Topical erythromycin vs blank vehicle in a multiclinic acne study; Jones EL et al.; A stable solution of erythromycin was developed using a vehicle of ethanol, propylene glycol, and citric acid buffer . In a controlled, randomized, double-blind comparison, a 2% solution of erythromycin applied to moderately severe facial acne was found to be superior to the blank vehicle in reducing the number of inflamed papules . During a period of 12 weeks, such papules were reduced by 56% in the erythromycin group, compared with 33% in the blank vehicle group . In the erythromycin group, 62% of the subjects had a good or excellent response, compared with 27% of those in the blank vehicle group . Adverse effects were similar in type in both groups and included redness, scaling, dryness, oiliness, burning, itching, and irritation of the eyes . No allergic reactions or skin infections were encountered.

Br J Clin Pharmacol, 1981 Aug, 12(2), 131 - 40
Absorption and bioavailability of oral erythromycin; Mather LE et al.; 1 Extent and rate of absorption of erythromycin were studied in 24 healthy volunteers whose disposition kinetics after i.v . injections had been previously documented . 2 Two clinically attractive oral dosage regimens were administered: erythromycin stearate tablets 1 h before meals (Regimen A), and erythromycin base capsules 30 min after start of meals (Regimen B), each equivalent to erythromycin 250 mg, 6 h apart for 9 doses . 3 Serum concentrations of erythromycin measured during the 1st and 9th (steady-state) dosing intervals resulted in higher maximum serum concentrations for Regimen A (median 1.1, range 0-3.3 and 2.7, 0.6-7.3 mg/l for Doses 1 and 9, respectively) compared with Regimen B (0.4, 0-2.2 and 1.4, 0.2-4.9 mg/l) . 4 Absorption occurred earlier with Regimen A with times to maximum concentrations (median, range) being 128, 60-greater than 360 and 118, 75-210 min for doses 1 and 9 respectively, (lag times 75, 15- greater than 360 and 73, 10-110 min) compared with 303, 130-greater than 360 and 173, 45-greater than 360 min (lag times 183, 70-greater than 360 and 190, 20-330 min) for Regimen B . 5 Where it could be assessed, absolute bioavailability for Regimen A was approximately 30% (Dose 1) and 65% (Dose 9) and 40% for both doses of Regimen B . 6 Whereas individual serum concentration-time curves were accurately predicted by the mean for Regimen A, predictability for Regimen B was impossible due to prolonged and variable lag time . 7 The large intersubject variability in erythromycin serum concentration after oral administration, has been shown conclusively to be related to variability in absorption kinetics and absolute bioavailability rather than to variability in disposition kinetics.

Antimicrob Agents Chemother, 1981 Aug, 20(2), 190 - 6
Influence of study design in assessing food effects on absorption of erythromycin base and erythromycin stearate; DiSanto AR et al.; We performed a series of six single-dose and multiple-dose studies to evaluate the effect of food on the absorption of erythromycin base and erythromycin stearate . When we used a single-dose design, we found that an unprotected erythromycin base preparation was absorbed extensively if a prolonged fast preceded administration of the drug . A shorter faster period (as occurs in clinical settings) dramatically reduced the absorption of unprotected base; however, film-coated tablets seemed to be as well protected as and were absorbed more rapidly than enteric-coated tablets when they were evaluated by single-dose testing procedures . In contrast, when a commercially available film-coated preparation of erythromycin base was evaluated in multidose fashion between meals (fasting), the drug was about 25% less well absorbed than commercially available enteric-coated base tablets . Finally, when commercially available film-coated erythromycin base and stearate formulations were administered with meals, both film-coated preparations were 43 to 59% less well absorbed than the enteric-coated base formulation . Furthermore, the enteric-coated base formulation performed equally well when administered either every 6 h between meals (fasting) or four times a day (immediately after meals and at bedtime) . These studies document the need for multidose bioavailability techniques when the bioavailabilities of acid-labile drugs are evaluated.

J Pharmacol Exp Ther, 1981 Aug, 218(2), 509 - 14
Self-induction by erythromycin of its own transformation into a metabolite forming an inactive complex with reduced cytochrome P-450; Danan G et al.; Erythromycin, 0.3 mM, elicited a small reverse type I binding spectrum with, and was slowly demethylated by, cytochrome P-450 from control rats . No absorption peak at 456 nm could be detected upon incubation of 0.3 mM erythromycin with NADPH and control microsomes . No complex formed in vivo could be detected in microsomes isolated 2 hr after a single dose of erythromycin, 2 mmol.kg-1 p.o . Repeated administration of erythromycin, 2 mmol.kg-1 p.o . daily for 4 days increased hepatic microsomal protein concentration, NADPH-cytochrome c reductase activity, the amplitude of the reverse type I binding spectrum of erythromycin and erythromycin demethylase activity . Microsomes isolated from rats treated with repeated doses of erythromycin exhibited a marked absorption peak at 456 nm . The absorption at 456 nm was further increased upon incubation with erythromycin and NADPH . It disappeared upon addition of 50 muM potassium ferricyanide . Disruption of the complex with potassium ferricyanide markedly increased the CO-binding capacity of dithionite-reduced microsomes . It further increased the amplitude of the reverse type I binding spectrum of erythromycin and erythromycin demethylase activity and increased ethylmorphine N-demethylase and benzo{a}pyrene hydroxylase activities . It is concluded that erythromycin induces its own transformation into a metabolite which forms a inactive 456-nm absorbing complex with the iron (II) of cytochrome P-450.

Biochim Biophys Acta, 1981 Jul 27, 654(2), 236 - 41
Competition between erythromycin and virginiamycin for in vitro binding to the large ribosomal subunit; Parfait R et al.; When the S component of virginiamycin binds in vitro to the 50 S ribosomal subunit, a change of fluorescence intensity proportional to the amount of complex formed occurs . Erythromycin competes with virginiamycin S for attachment to ribosomes, and removes previously bound virginiamycin S from its target, as revealed by spectrofluorimetric analysis . The 50 S subunits which are incubated with the M component of virginiamycin (50 S*) have an increased affinity for virginiamycin S (the association constants of virginiamycin S with ribosomes are 2.5 x 10(6) M-1 in the absence of virginiamycin M, and 15 x 10(6) M-1 in its presence) . Erythromycin does not compete with virginiamycin S for attachment to 50 S* subunits nor is it able to remove virginiamycin S previously bound to the 50 S* subunit . Thus, virginiamycin M produces a change in ribosomes, which results in a tighter complex virginiamycin S-50 S* subunit . Such change does not require the presence of virginiamycin M, however, as shown by the observation that ribosomes to which labeled virginiamycin M is transiently linked bind virginiamycin S in a form that cannot be removed by erythromycin.

Avian Dis, 1981 Jul-Sep, 25(3), 768 - 78
Sequential pathology of genital tract in chickens experimentally infected with Mycoplasma gallisepticum; Pruthi AK et al.; Unsexed day-old White Leghorn chicks hatched from eggs pre-treated with erythromycin were infected via the yolk sac with a 48-hr broth culture of pathogenic Mycoplasma gallisepticum (S6) . Fourteen of the 57 experimental female birds had gross lesions in the oviduct, characterized by the presence of grayish-white caseous plugs of various sizes in a segment or throughout the length of the oviduct . Forty-six of the infected female birds had microscopic lesions, detected primarily as mild heterophilic infiltration, lymphocytic aggregates, lymphoid follicles, diffuse lymphocytic infiltration, pleocellular response, or a combination of any of these depending on the stage and extent of infection . The caseous plugs were formed by tissue debris, fibrin, necrotic heterophils, and sometimes a few lymphocytes and macrophages . Changes that accompanied the necrotic exudate were atrophy of the mucosa, hypertrophy of the oviduct wall, or sometimes necrosis of the folds of mucosa . No significant gross and microscopic lesions were detected in ovaries, although 3 of the 33 infected male chickens had histological lesions in the testes . Gross and microscopic changes of mycoplasmosis were also found in the respiratory tract . M . gallisepticum could be consistently reisolated from oviduct(s) up to five weeks PI; thereafter, isolations were intermittent . From the ovaries or testes the organism could be isolated consistently up to one week PI only . Agglutinins were detected in the sera of infected chickens as early as one week PI, when the mean titer was 1:5, and it reached a maximum of 1:128 at six weeks PI . Thereafter the titer gradually declined, but the demonstrable agglutinins were present until 25 weeks PI.

Sex Transm Dis, 1981 Jul-Sep, 8(3), 220 - 1
In vitro activity of clindamycin against Chlamydia trachomatis; Bowie WR; Clindamycin hydrochloride was moderately active in vitro against Chlamydia trachomatis when it was added to the culture system 1 hr, but not 48 hr, after inoculation of test organisms . Clindamycin is almost as active in vitro against C . trachomatis as is erythromycin in vitro; this finding suggests that clindamycin might have clinically significant activity in vivo.

J Pediatr, 1981 Jul, 99(1), 153 - 6
Effect of erythromycin on theophylline clearance in asthmatic children; LaForce CF et al.; Fifteen asthmatic children (mean age = 14.5 years) who required daily theophylline therapy were studied for effect of erythromycin ethyl-succinate on theophylline clearance . After a one week course of EES, there was 25.8 +/- 18.4% reduction in theophylline clearance rate (P less than 0.001), and a concomitant elevation in steady-state serum theophylline concentration of 40.0 +/- 35.3% (P less than 0.01) . Three subjects reached serum theophylline concentrations greater than 20 micrograms/ml . Patients receiving therapeutic doses of theophylline are at considerable risk of theophylline toxicity if EES is co-administered.

Nucleic Acids Res, 1981 Jun 11, 9(11), 2549 - 62
Characterization of a plasmid-specified ribosome methylase associated with macrolide resistance; Shivakumar AG et al.; The ermC gene of plasmid pE194 specifies resistance to the macrolidelincosamide-streptogramin B antibiotics . This resistance, as well as synthesis of the 29,000 dalton protein product of ermC, has been shown to be induced by erythromycin . Weisblum and his colleagues have established that macrolide resistance is associated with a specific dimethylation of adenine in 23 S rRNA . We show that pE194 specifies an RNA methylase that can utilize either 50 S ribosomes or 23 S rRNA as substrates . Synthesis of this methylase is induced by low concentrations of erythromycin, and the enzyme is produced in elevated amounts by strains carrying a high copy number mutant of pE194 . The methylase comigrates with the 29K ermC product on polyacrylamide gels . The purification and some properties of this methylase are described.

Antibiotiki, 1981 Jun, 26(6), 407 - 10
{Exclusion of propyl alcohol from the medium for culturing the erythromycin producer}; Gruzina VD et al.; Propyl alcohol is a precursor of erythromycin . It is one of the components of the medium for production of the antibiotic . Still, this raw material has an unfavorable effect on employees and is fire hazardous . The results of the development of the erythromycin-producing organism are presented . A strain requiring no propyl alcohol as a precursor in the medium and producing the same amounts of the antibiotic was obtained by means of step-wise selection with the use of a mutagen.

Surgery, 1981 Jun, 89(6), 683 - 6
Risk factors in colostomy closure; Varnell J et al.; A retrospective study of 69 patients who underwent colostomy closure between 1973 and 1978 was conducted to evaluate three categories of risk: predisposing risk factors, preoperative interventions, and intraoperative techniques . The overall morbidity rate was 44% with no deaths . Factors associated with a greater complication rate included a divided colostomy (especially Hartmann's pouch), diverticulitis, elderly patients, and lack of preoperative oral antibiotics . Irrigation of the distal segment in divided colostomies and preoperative use of systemic antibiotics in association with oral agents, particularly neomycin-erythromycin, may be effective in decreasing morbidity . Factors that did not influence morbidity included time between colostomy and closure, wound management intraoperatively, the use of systemic antibiotics alone, and the location of loop colostomies . With careful preparation of the patient to combat the documented risk factors, colostomy closure may be safely undertaken in most patients.

Chest, 1981 Jun, 79(6), 669 - 71
Legionnaires' disease following cardiac transplantation; Copeland J et al.; The first two cases of Legionnaires' disease in heart transplant patients are reported . Of interest in these cases were culture of the organism from sputum, diagnosis by percutaneous lung aspiration, bronchopleural fistula formation in the first case, which was then successfully treated with multiple-tube thoracostomies, early cavitation of lesions in both cases after the start of antibiotic therapy, positive direct fluorescent antibody staining from transtracheal aspirate 42 days after starting appropriate antibiotic therapy in the first case, apparent superiority of intravenous erythromycin therapy in the first case, and survival of both patients . Our laboratory isolated and identified the organism in both cases.

Boll Ist Sieroter Milan, 1981 May, 60(2), 95 - 101
{Epidemiology of multiresistant S . aureus in a burn center}; Somenzi P et al.; Multi-resistant S . aureus, have been isolated from wounds of patients in the burn unit of the University of Parma . The strains were resistant to penicillin (85%), methicillin (30%), gentamycin (63%), rifampicin (41%), cotrimoxazole (38%), lincomycin (39%), tetracycline (73%), erythromycin (66%) and cephaloridine (11%) . The spread of these strains has been monitored by the analysis of the antibiograms and the lysotypes and in few cases some strains were also found in other wards of the Hospital . All of these had some correlation with the burns unit . Medical and technical staff of this ward was found to be carrier of multi-resistant S . aureus in 46% of the cases and that feature is supposed to be the most important in the epidemiology of S . aureus in this Hospital.

Arch Intern Med, 1981 May, 141(6), 741 - 2
Pulmonary function after adult respiratory distress syndrome associated with Legionnaires' disease pneumonia; Shaw RA et al.; Two patients with adult respiratory distress syndrome (ARDS) caused by Legionnaires' disease were treated with erythromycin lactobionate, and they survived . Sequential pulmonary function studies and chest roentgenograms were obtained in both patients . Despite previous suggestions that severe fibrosis might complicate the recovery of patients with this disease, both patients had normal lung volumes and only minimal reduction in single-breath carbon monoxide diffusing capacity ten weeks after the onset of the disease . Thus, pulmonary function after ARDS caused by Legionnaires' disease seems to be only minimally disturbed.

Clin Pharmacol Ther, 1981 May, 29(5), 601 - 5
Effect of erythromycin base on theophylline kinetics; Zarowitz BJ et al.; Because of several recent reports describing altered theophylline elimination in the presence of salts of erythromycin, the effect of a 10-day course of erythromycin base on theophylline kinetics was studied in eight healthy adult men . Theophylline (4 mg/kg) was given on four separate study days: (1) prior to starting erythromycin, (2) on the third day of erythromycin administration, (3) on the tenth day of erythromycin administration, and (4) 2 weeks after the course of erythromycin was completed . Mean theophylline kinetic parameter values on each of the 4 study days were: apparent volume of distribution (Vd), 0.466, 0.466, 0.472, and 0.470 1/kg; elimination half-life (t1/2), 7.4, 7.8, 8.5, and 7.0 hr; and total body clearance (ClB), 0.747, 0.723, 0.683, and 0.821 ml/min/kg . A maximum decrease of 20.7% in theophylline ClB was noted by the third study day . Two weeks after erythromycin was discontinued, the greatest increase in ClB observed was 45.7% . Differences in t1/2 and ClB between the third and fourth study days were statistically significant (p less than 0.05).

JAMA, 1981 May 1, 245(17), 1758 - 9
Pretibial rash in Legionella pneumophila pneumonia; Helms CM et al.; Legionella pneumophila pneumonia developed in a 46-year-old man, 23 days after receiving a cadaveric renal homograft . A painful, nonpruritic, macular, erythematous rash limited to the pretibial surfaces of both legs appeared on the fifth day of illness . Fever, pneumonia, and rash resolved in association with erythromycin lactobionate therapy.

Antimicrob Agents Chemother, 1981 May, 19(5), 736 - 9
Pharmacokinetics of erythromycin ethylsuccinate and estolate in infants under 4 months of age; Patamasucon P et al.; We studied the pharmacokinetics of erythromycin estolate and ethylsuccinate suspensions in infants under 4 months of age who were being treated for chlamydial infections or pertussis . We conducted our studies after the initial dose of 10 mg/kg and subsequently during steady-state treatment . The estolate preparation resulted in higher peak concentrations in sera, and its absorption and elimination half-lives were longer . Peak concentrations occurred 3 h after a dose with the estolate preparation and 1 h after a dose with the ethylsuccinate preparation . The area under the curve for the estolate preparation was about three times greater than that for the ethylsuccinate preparation . Based on these findings, we recommend that erythromycin estolate suspensions be given to young infants at 8- or 12-h intervals (30 mg/kg per day in three divided doses or 20 mg/kg per day in two divided doses) and that erythromycin ethylsuccinate is best given at 6-h intervals (40 mg/kg per day in four divided doses).

Drug Intell Clin Pharm, 1981 May, 15(5), 372 - 6
Clinical trial of topical erythromycin in inflammatory acne; Prince RA et al.; Sixty-nine informed subjects participated in a split-face, double-blind trial of topical erythromycin base 2% in Vehicle/N versus Vehicle/N alone . All subjects had grades II or III acne as described by Pillsbury . Study solutions were assigned to a randomly selected side of the subject's face . Solutions were applied twice daily . Inflammatory lesion counts were performed by the same investigator during the eight weeks of study at biweekly intervals . The difference in inflammatory lesion counts from beginning to end of study for each side of the face was compared utilizing Student's paired t-test . There was not a statistically significant difference in mean inflammatory lesions at the end of eight weeks (D = 1.46, t = 1.36, df 68) . There was, however, a significant difference at two and six weeks (D = 2.59, t = 3.72, df 68; D = 1.41, t = 2.03, df 68) . Observed differences in lesion counts were not considered to be clinically significant.

Boll Soc Ital Biol Sper, 1981 Apr 30, 57(8), 900 - 3
{Effect of pretreatment with bacterial endotoxin on erythromycin estolate-induced cholestasis}; Adinolfi L et al.; The effect of acute and chronic endotoxin (LPS) treatment on the erythromycin estolate (EE) induced cholestasis, was studied using the isolated perfused rat liver . Addition of EE markedly reduced bile and perfusate flows in livers from control rats but did not alter these parameters in livers from endotoxin pretreated rats or in vitro treated with LPS . We suggest that changes in membrane organization induced by LPS may alter the diplay of EE toxicity.

Postgrad Med, 1981 Apr, 69(4), 87 - 92
Legionnaires' disease with severe hypoxemia and saddleback fever; Shankar PS et al.; In the case of Legionnaires' disease described, severe respiratory problems necessitated mechanical ventilatory support, tracheal intubation, and positive end-expiratory pressure . Fever was eliminated with erythromycin therapy but returned after five days, and lung infiltrates spread . After supplementary treatment with other antibiotics and methylprednisolone sodium succinate, both the fever and the infiltrates disappeared . We feel that the multisystem involvement and the recrudescence of fever in our patient emphasize the wide spectrum of characteristics of Legionnaires' disease and the importance of continuation of antibiotics for a prolonged period to eradicate infection.

Mol Cell Biol, 1981 Apr, 1(4), 321 - 9
Effects of mycoplasma contamination on phenotypic expression of mitochondrial mutants in human cells; Doersen CJ et al.; HeLa cells sensitive to the mitochondrial protein synthesis inhibitors erythromycin (ERY) and chloramphenicol (CAP) and HeLa variants resistant to the effects of these drugs were purposefully infected with drug-sensitive and -resistant mycoplasma strains . Mycoplasma hyorhinis and the ERY-resistant strain of Mycoplasma orale, MO-ERYr, did not influence the growth of HeLa and ERY-resistant ERY2301 cells in the presence or absence of ERY . M . hyorhinis also did not affect the growth of HeLa and CAP-resistant Cap-2 cells in the presence or absence of CAP . However, both HeLa and Cap-2 cells infected with the CAP-resistant strain of M . hyorhinis, MH-CAPr, were more sensitive to the cytotoxic effect of CAP . This may be due to the glucose dependence of the cells, which was compromised by the increased utilization of glucose by MH-CAPr in these infected cell cultures . In vitro protein synthesis by isolated mitochondria was significantly altered by mycoplasma infection of the various cell lines . A substantial number of mycoplasmas copurified with the mitochondria, resulting in up to a sevenfold increase in the incorporation of {3H}leucine into the trichloroacetic acid-insoluble material . More importantly, the apparent drug sensitivity or resistance of mitochondrial preparations from mycoplasma-infected cells reflected the drug sensitivity or resistance of the contaminating mycoplasmas . These results illustrate the hazards in interpreting mitochondrial protein synthesis data derived from mycoplasma-infected cell lines, particularly putative mitochondrially encoded mutants resistant to inhibitors of mitochondrial protein synthesis.

Sem Hop, 1981 Mar 8-15, 57(9-10), 499 - 500
{Acute respiratory distress syndrome: indigenous Legionnaires' disease (author's transl)}; Becq-Giraudon B et al.; The possibility of indigenous Legionnaires' disease should be known as suggested by the following case : a 69-year-old man, diabetic, having never travelled out of Poitou, suffers from serious pneumonia with dyspnea needing mechanical ventilation with positive end-expiratory pressure . After failure of ampicillin, the evolution seems favourable with cotrimoxazole . However the discontinuation of this last drug is followed by a relapse which is treated with success by erythromycin . Serodiagnoses will be positive for Legionella Pneumophila serogroup I . This case, typical by its clinical features, makes itself noticed by its epidemiology and the relapse under cotrimoxazole, proving that erythromycin remains the choice antibiotic for these infections.

Arch Dis Child, 1981 Mar, 56(3), 193 - 8
Persistence of chlamydial infection after treatment for neonatal conjunctivitis; Rees E et al.; A high incidence of pharyngeal infection was found in babies with isolation-positive chlamydial conjunctivitis . Chlamydia trachomatis was isolated from the pharynx of 12 (52%) of 23 babies before treatment, and was reisolated from the eyes of 4 (12%) of 34 and from the pharynx of 14 (41%) of 34 after treatment . C trachomatis was reisolated significantly more often from babies treated only with topical tetracycline for 4 weeks (75%) than from those treated with both topical tetracycline and oral erythromycin for 2 weeks (32%) . Reisolation from the eyes was associated with only minor clinical signs . Radiological signs of an inflammatory lesion in the chest were found in 2 of 8 babies examined because of persistent cough . These signs were not associated with high or rising titres of serum chlamydial antibody.

Fortschr Med, 1981 Feb 26, 99(8), 245 - 8
{Present aspects of syphilis: 2 . Serology, therapy}; Krause H; The actual aspect of syphilis in the Federal Republic of Germany is determined by epidemiology, treponemal specific serodiagnosis and modern therapy . Compared with the frequency after the last war, syphilis diminished to a level of 5-10 per cent at present . In particular, connatal, tertiary and neuro-syphilis have decreased absolutely and relatively . In serodiagnostics of lues venerea the first tests to be used are the indirect hemagglutination-test TPHA and the quantitative lipoidal test VDRL . In case of reactive results in one of these methods, the FTA-ABS-test and furthermore the TPI-test are applied for verification . The treponemal specific IgM-diagnosis (IgM-FTA-ABS, IgM-19 S-FTA) permits a statement on the acuteness of the syphilitic process and control of the course after treatment . In current chemotherapy of syphilis penicillin ranges in the first place followed by tetracyclines and erythromycin.

Am J Med Sci, 1981 Jan-Feb, 281(1), 2 - 13
Legionnaires' disease among pneumonias in Iowa (FY 1972-1978) II . Epidemiologic and clinical features of 30 sporadic cases of L . pneumophila infection; Helms CM et al.; We reviewed retrospectively the clinical records of 30 cases of sporadic Legionella pneumophila infection that occurred in Iowa between FY 1972 and 1978 . Cases occurred throughout the year, most between May and December . Twenty-one male patients and 9 female patients ranging in age from 5-80 years were infected . Half the patients smoked or had an underlying illness; five were receiving corticosteroids or immunosuppressive therapy . Occupations and exposures related to hospitals, construction and travel were common; four patients had been exposed to birds . In addition to L . pneumophila infection, six patients had evidence of infection with a viral, mycoplasmal, bacterial, mycobacterial or fungal pathogen; three had had preceding dental infections . Twenty-seven cases were pneumonias visible on radiographs . Fever, cough, chills, myalgia and rales occurred inover half the cases . Headache, gastrointestinal symptoms and encephalopathy also were seen . Upper respiratory symptoms were uncommon . Urinalysis and blood studies often suggested renal and hepatic involvement, but other routine laboratory diagnostic tests were not helpful . All but two patients were hospitalized; seven required intensive care . The median duration of hospitalization was 12 days . Two patients who did not receive erythromycin or tetracycline therapy died.

Ann Rech Vet, 1981, 12(3), 321 - 6
{Bioavailability of erythromycin and colistin in calves (author's transl)}; Escoula L et al.; Bioavailability of erythromycin and colistin was studied in plasma, ruminal liquid and nasal mucus after simultaneous injection by intraruminal or intramuscular route . After intramuscular injection, erythromycin was found in plasma and respiratory tract, colistin in plasma . After oral administration, only erythromycin was found in nasal cavity secretions but nitrogen metabolism and volatile fatty acid production were modified in rumen.

J Int Med Res, 1981, 9(6), 470 - 7
The bioavailability of erythromycin stearate versus enteric-coated erythromycin base when taken immediately before and after food; Clayton D et al.; 1 . Erythromycin plasma concentrations were determined in twenty subjects after a single dose, immediately before food, of erythromycin, 500 mg . as: (1) erythromycin stearate (Erythrocin, 500 mg, ovaloid tablets), and (2) erythromycin base (Eryc, 250 mg, capsules containing enteric-coated pellets) . 2 . Plasma concentrations were again determined in eighteen of the original subjects with the same dose given immediately after food . 3 . Maximum Plasma Concentrations (mcg/ml) (See formula in text) 4 . Erythromycin stearate was more bioavailable than erythromycin base when administered immediately before food . The preparations were bioequivalent when given immediately after food.

Scand J Infect Dis, 1981, 13(3), 211 - 5
Absorption of erythromycin from pediatric suspension in infants and children; Eriksson M et al.; The absorption of erythromycin in infants and children was estimated after the administration of an erythromycin suspension . The subjects were divided into 3 age groups: 0-1 month, 1-6 months and 6 months-6 years . The absorption was lower in infants less than 1 month of age than in the older children . Erythromycin ethylsuccinate and erythromycin stearate were equally well absorbed in the fasting state in subjects 6 months-6 years of age . Administration of the drug at mealtimes considerably increased the absorption of erythromycin ethylsuccinate but had little effect on the absorption of erythromycin stearate . The absorption of erythromycin stearate in the fasting state was much lower than that of erythromycin ethylsuccinate in infants 1-6 months of age . None of the infants given erythromycin ethylsuccinate because of an outbreak of whooping-cough on the neonatal ward showed evidence of liver toxicity, nor did they develop symptoms of whooping-cough.

Duodecim, 1981, 97(5), 231 - 4
{Actinomycosis and IUD's}; Purola E et al.; PIP: The use of IUDs can contribute to the incidence of actinomycosis . Actinomycosis, formerly regarded as a fungal disease, is now known to be caused by bacteria of the genus Actinomyces . The diagnosis of actinomycosis is difficult because the disease usually does not manifest itself in any specific symptoms . The most common diagnostic method uses histological slides . It is difficult to do cultures, and they require good anaerobic techniques . Pap smears are usually reliable but not unambigous since, in a heavy concentration of bacteria, Actinomyces may be mistaken for similar organisms . More specific results can be obtained using immunofluorescence . Before 1973, actinomycosis was considered a rare disease, a secondary one often resulting from an outbreak of appendicitis . Now it is commonly believed that women who have worn a plastic IUD for at least 2 years, and possibly women whose copper IUDs have not been changed for some time, are highly susceptible to actinomycosis . The 1st case of genital actinomycosis was discovered in 1973, with 10 cases reported in 1975 in which the patients had been using IUDs for at least 2 years . In 1979, 2 deaths from genital actinomycosis were reported . Also in 1979, a study reported actinomycosis in 19% of 330 women using IUDs . 1980 study found the disease in 40 of 128 women using plastic IUDs and 2 out of 165 women using copper IUDs for over 2 years . In Finland, physicians have always favored copper IUDs and frequent changes of any kind of IUD . A Swedish physician advocated in 1980 that all plastic IUDs be removed, that copper IUDs be changed frequently, and that no IUD be inserted if any gynecological infection is present . Annual pap smears are advisable and, only where necessary, antibiotics should be taken and IUDs removed . Actinomycosis can be cured with penicillin, tetracyclines, and erythromycin .

Ciba Found Symp, 1981, 85, 151 - 71
Ototoxic drugs and noise; Brown RD et al.; Drugs that produce tinnitus can be subdivided into those which produce temporary or permanent hearing loss and those which apparently do not cause any hearing loss . The tinnitus occurring with drugs of the first group is probably secondary to the hearing loss . However, most of the drugs that produce tinnitus without an accompanying hearing loss probably do so because of their effect on biogenic amines in the central nervous system and/or as an extension of their proconvulsant side-effects . A pre-existing cochlear impairment is the underlying factor in most patients who experience tinnitus . Not only can ototoxic drugs or high levels of noise produce cochlear impairment but the interaction of the two can place humans in more jeopardy than when exposed to either agent alone . Chloramphenicol has little ototoxic potential when administered systemically in humans . However, our studies show that when chloramphenicol is combined with noise exposure in rats, considerably more cochlear damage results than from the noise alone (chloramphenicol alone does no produce any cochlear damage) . We are presently conducting more detailed studies of this ototoxic interaction to determine whether it occurs with other antibiotics (such as erythromycin) which are also commonly considered to have minimal ototoxicity.

Int J Oral Surg, 1981, 10(Suppl 1), 198 - 202
Comparison of serum erythromycin concentration following administration of 100 mg erythromycin ethyl succinate intramuscularly and 500 mg erythromycin stearate orally; McGimpsey JG et al.; Serum erythromycin concentrations were estimated following administration of 100 mg erythromycin ethyl succinate intramuscularly and 500 mg erythromycin stearate orally . The subjects (30 healthy students) were randomly divided into two groups and each subject received a single dose of the alternate form of the drug after a 4-week interval . Blood samples were obtained at 0.5, 1, 1.5, 2, 3 and 4 h after administration by separate venepuncture . All 30 subjects recorded serum levels above 0.2 microgram/ml following administration of the intramuscular form of the drug . Following administration of the oral form of the drug, five subjects failed to record serum levels above 0.2 microgram/ml by the 2-h sampling time and three failed to do so by the 4th hour . It is concluded from the results that, despite the high serum levels recorded with the oral form when taken with food, the intramuscular route gives a greater assurance of consistent absorption into the blood stream . This result suggests that the use of the oral form of the drug as a prophylactic antibiotic in patients receiving dental treatment remains in doubt.

Dermatologica, 1981, 162(5), 342 - 9
Effect of systemic erythromycin stearate on the inflammatory lesions and skin surface fatty acids in acne vulgaris; Bleeker J et al.; Publication Types:

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