Erythromycin

Drug Metab Dispos, 1990 Sep-Oct, 18(5), 595 - 606
Cyclosporin A drug interactions . Screening for inducers and inhibitors of cytochrome P-450 (cyclosporin A oxidase) in primary cultures of human hepatocytes and in liver microsomes; Pichard L et al.; In previous papers we demonstrated that cyclosporin A (CsA) was specifically oxidized in rabbit and human liver by cytochrome P-450IIIA . We therefore anticipated that any drug that is an inducer or an inhibitor of this cytochrome should lead to interaction with CsA when given in association with it . In order to confirm this hypothesis, primary cultures of human hepatocytes and human liver microsomes were used to "reproduce" in vitro clinically significant interactions observed between CsA and drugs known either as specific inducers (i.e., rifampicin) or as specific inhibitors (i.e., erythromycin) of P-450IIIA . Our results were in close agreement with the clinical reports . Human hepatocytes maintained in primary cultures for 72 hr in the presence of 50 microM rifampicin exhibited increased levels of P-450IIIA, determined by Western blot using specific antibodies, and concomitant increase in CsA oxidase activity, determined by HPLC analysis of extra and intracellular media . Conversely, these cultures exhibited erythromycin concentration-dependent decreases in CsA oxidase activity when incubated in the presence of 5, 20, and 100 microM erythromycin . In addition, a Lineweaver-Burk analysis of the erythromycin-mediated inhibition of CsA oxidase activity in human liver microsomes revealed competitive inhibition (with Ki of 75 microM) as expected, this macrolide being a specific substrate of P-450IIIA . Using this experimental approach, 59 molecules representative of 17 different therapeutic classes were screened for inducers and inhibitors of CsA oxidase activity . Our results allowed us to elucidate the molecular mechanism of previously observed, but unexplained, drug interactions involving CsA, and to detect drugs that should interfere with CsA metabolism as inducers or inhibitors . Drugs detected as potential inducers of CsA oxidase included: rifampicin, sulfadimidine, phenobarbital, phenytoin, phenylbutazone, dexamethasone, sulfinpyrazone, and carbamazepine . Drugs detected as potential competitive inhibitors included: triacetyloleandomycin, erythromycin, josamycin, midecamycin, ketoconazole, miconazole, midazolam, nifedipin, diltiazem, verapamil, nicardipine, ergotamine, dihydroergotamine, glibenclamide, bromocriptine, ethynylestradiol, progesterone, cortisol, prednisone, prednisolone, and methylprednisolone . Finally, cefoperazone, cefotaxime, ceftazidime, isoniazide, doxycycline, spiramycin, sulfamethoxazole, norfloxacin, pefloxacin, vancocin, trimethoprim, amphotericin B, valproic acid, quinidine, cimetidine, ranitidine, omeprazole, diclofenac, aspirin, paracetamol, debrisoquine, guanoxan, captopril, furosemide, acetazolamide, sparteine, gliclazide, and imipramine were found not to interfere with the hepatic metabolism of CsA.

Biochim Biophys Acta, 1990 Aug 27, 1050(1-3), 197 - 202
The extension of polyphenylalanine and polylysine peptides on Escherichia coli ribosomes; Hardesty B et al.; Fluorescence techniques were used to examine aminoacyl-tRNA binding to Escherichia coli ribosomes and the subsequent extension of polyphenylalanine and polylysine nascent peptides . The results demonstrate that deacylated tRNA, an analogue of peptidyl-tRNA and puromycin (an analogue of aminoacyl-tRNA) can be bound simultaneously to the same ribosome . Moreover, the fluorescence properties of nascent polyphenylalanine and polylysine peptides with a fluorophore attached to their amino termini were determined and found to be quite different . This difference is reflected in the effects that erythromycin has in each case.

Med Klin (Munich), 1990 Aug 15, 85(8), 481 - 4
{Therapy of bullous pemphigoid with erythromycin}; Mensing H et al.; Bullous pemphigoid is the most common autoimmune mediated bullous disease in men . Erythromycin combined with a low dose methylprednisolone was tested in eleven patients in a prospective study . A historical collective of the last 33 patients treated before this study was started served as the control group . The duration of hospitalization as an expression of therapeutic response, but also of lowered side effects dropped down from 43 to 33 days in the erythromycin treated group . The study further shows a responder rate of about two thirds of the patients, one third, however, required a high dose regimen of corticosteroids in order to ameliorate . From this could be concluded, that two different subtypes of bullous pemphigoid exist concerning their therapeutic response.

Tidsskr Nor Laegeforen . 1990 Aug 10;110(18):2359.
{Ergotamine induced ischemia}; Remme A et al.; Drugs containing ergotamine are commonly used in the treatment of migraine . Hypersensitivity to these drugs may be triggered off even with intake of recommended doses, inducing peripheral ischemia . Contributing factors to ergotism are concurrent fever, liver disease and drugs such as erythromycin or propranolol . We present a case history and different methods of treatment.

Dtsch Med Wochenschr, 1990 Aug 3, 115(31-32), 1188 - 92
{Persisting alveolitis after Legionella pneumonia}; Hurter T et al.; Pneumonia was diagnosed radiologically in three patients (43, 54 and 58 years old, respectively), presenting with temperatures between 39 degrees and 40 degrees C, cough and weight loss . These signs persisted for 6, 7 and 13 weeks, respectively, but the pathogens could not be cultivated . Lung function analysis showed partial respiratory insufficiency with extensive restrictive impairment of ventilation . Samples of lung tissue were obtained in all three cases and histology revealed fibrosing alveolitis . In two patients serology yielded antibody titres of 1:512 and in one patient of 1:128, against Legionella pneumophila . Treatment with 1 g erythromycin three times daily was unsuccessful . Therefore, the patients were given prednisone at an initial dosage of 50-100 mg which was subsequently reduced . Lung function normalised during this treatment course, radiological findings and antibody titres receded . Hence, treatment with corticosteroids should be attempted if there is an urgent suspicion of fibrosing alveolitis caused by Legionella pneumophila, after having excluded a florid infectious pneumonia and after failure of erythromycin treatment.

Mol Pharmacol, 1990 Aug, 38(2), 207 - 13
Studies on the expression and metabolic capabilities of human liver cytochrome P450IIIA5 (HLp3); Wrighton SA et al.; The human P450III family has been shown to be composed of at least four members, P450IIIA3 (HLp), P450IIIA4 (P450NF), P450IIIA5 (HLp3), and P450IIIA6 (HLp2) . Due to the lack of probes that specifically recognize the individual members of this family, little is known about their relative expression . We prepared a form-specific antibody to P450IIIA5 by immunoabsorption of anti-P450IIIA5 IgG against Sepharose 4B upon which microsomes that did not contain P450IIIA5 or purified P450IIIA3 had been bound . Immunoblot analyses demonstrated that P450IIIA5 was expressed at detectable levels in only 19 of 66 (29%) human livers . The expression of P450IIIA5 was not influenced by the gender or medical history of the patients . When the expression of P450IIIA5 in different age groups was examined, it was observed that P450IIIA5 was detected in a statistically significantly higher percentage of children and adolescents (19 years old and under), as compared with the remaining population (8 of 17, 47%, versus 11 of 46, 24%, respectively) . Furthermore, P450IIIA5 was detected in 1 of 10 human fetal livers . Of the large number of compounds identified as substrates of P450III family members, P450IIIA5 was found to actively metabolize nifedipine, testosterone, estradiol, dehydroepiandrosterone 3-sulfate, and cortisol, whereas it metabolized poorly or did not metabolize erythromycin, quinidine, 17 alpha-ethynylestradiol, and aflatoxins . The acetylenic steroid gestodene was found to be an effective mechanism-based inhibitor of both P450IIIA4 and P450IIIA5 . Immunoblots of microsomes isolated from untreated and dexamethasone-, phenobarbital-, or 3-methylcholanthrene-treated HepG2 cells that were developed with an antibody that recognizes all the P450III family members demonstrated that no proteins in the P450III family were expressed by the HepG2 cells . In conclusion, our studies indicate that P450IIIA5 is polymorphically expressed at all stages of human development and is more limited in its metabolic capabilities than is P450IIIA4.

Biochem Pharmacol, 1990 Aug 1, 40(3), 637 - 42
The in vivo induction of rat hepatic cytochrome P450-dependent enzyme activities and their maintenance in culture; Hammond AH et al.; Cytochrome P450-dependent enzyme activities were measured in hepatocytes from adult male rats, induced in vivo with phenobarbitone, beta-naphthoflavone, dexamethasone or isoniazid: the stability of the induced activities in culture was also determined . Each inducer produced a characteristically different pattern of enzyme activities with dexamethasone, isoniazid and beta-naphthoflavone selectively inducing erythromycin N-demethylase, p-nitrophenol hydroxylase and ethoxyresorufin O-dealkylase respectively . In general, the induced activities were maintained for 24 hr in culture . This indicates the feasibility of an in vivo induction-hepatocyte culture system for the study of metabolism-mediated toxicity.

Antibiot Khimioter, 1990 Aug, 35(8), 14 - 6
{Pharmacological availability of erythromycin granules for children's use}; Korenev SV et al.; Pharmaceutical availability of erythromycin granules with polymeric coating of different composition+ was studied . With an account of the ++anatomo-physiological features of a child organism and the properties of the antibiotic, acetylphthalyl cellulose in combination with hydroxypropyl methylcellulose or methyl cellulose was used as a film forming agent . The coated granules were estimated by such parameters as the time of disintegration and the rate of dissolution in various media . The results of the study showed that coating of the erythromycin granules with the film composed of acetylphthalyl cellulose and hydroxypropyl methylcellulose in the ratio of 8 to 2 provided the required protection of the antibiotic in acid media and high pharmaceutical availability of the drug.

Biochem Int, 1990 Aug, 21(5), 909 - 14
Co-operative binding of ribosomal proteins to an erythromycin affinity column; Pye DA et al.; The binding of the E . coli ribosomal proteins L4, L5 and L21 to an erythromycin affinity column has been found to be co-operative . Binding does not occur in the absence of other ribosomal proteins.

Singapore Med J, 1990 Aug, 31(4), 378 - 80
The management of chronic non-gonococcal urethritis; Cheong WK; Non-gonococcal urethritis (NGU) is one of the most common sexually transmitted diseases today . Oral tetracyclines and erythromycin are well established choices of treatment . Despite adequate treatment, about 30-35% of NGU persist or recur . The cause of persistence or recurrence remains unknown . Prostate gland involvement has to be ruled out where indicated . A 4 to 6 week course of tetracyclines or erythromycin is suggested for persistent or recurrent NGU . Counselling to emphasize that chronic NGU is probably a self limited disorder would be of help.

Nihon Kyobu Shikkan Gakkai Zasshi, 1990 Aug, 28(8), 1066 - 71
{Effect of erythromycin on the generation of neutrophil chemiluminescence in vitro}; Hirata T et al.; In order to elucidate the therapeutic mechanisms of low dose-long term erythromycin (EM) therapy in patients with diffuse panbronchiolitis (DPB), the authors evaluated the effect of in vitro EM treatment on neutrophil (PMN) oxygen radicals production . EM has potent capacity to suppress PMN chemiluminescence (CL) induced by the N-formyl Met-leu-phe (FMLP), opsonized zymosan, and calcium ionophore A23187 stimulation . In marked contrast, phorbol myristate acetate (PMA)-induced PMN CL were much less affected by EM treatment . The suppressive activity of EM was dependent on the EM concentration and at a EM concentration of 25 micrograms/ml, FMLP-induced PMN CL were suppressed by 45.3 +/- 5.6% (n = 7), but PMA-induced CL were suppressed only marginally, 11.9 +/- 3.7% (n = 7) . The onset of inhibitory activity of EM is rapid and at 5 min., 60.1% of the maximum suppression at 60 min . was observed . This EM-induced suppression was found to be reversible and dependent on the EM-pretreatment temperature since the suppressive activity of EM were observed only at 37 degrees C but not at 0 degrees C . These results suggest that actively transported intracellular EM exerts its suppressive activity by inhibiting the process of Ca++ transfer or Ca++ utilization by cells . In addition, these results were consistent with the concept that EM might act as an anti-inflammatory agent in chronic bacterial airway infections such as bronchiectasis and DPB where the PMN appear to play an important role in the generation of airway destruction.

J Am Acad Dermatol, 1990 Aug, 23(2 Pt 1), 269 - 79
Cutaneous surgery and the pregnant patient; Gormley DE; Cutaneous surgery in 34 pregnant women is described . The main indication for surgery was the diagnosis and/or treatment of malignancy . Surgery during the period of organogenesis (15 to 56 days) should be avoided when possible . Patients should be positioned on the left side during the procedure to avoid the supine hypotensive syndrome . Monitoring of the fetal heartbeat is desirable . Local anesthetics, penicillin, and erythromycin are safe if used carefully . Acetaminophen is the analgesic of choice . Exposure to the sun should be avoided during the perioperative period.

Arch Dermatol, 1990 Aug, 126(8), 1064 - 7
Disseminated Mycobacterium chelonae subspecies chelonae infection with cutaneous and osseous manifestations; Drabick JJ et al.; A 75-year-old man who had been receiving corticosteroids for treatment of chronic obstructive pulmonary disease presented with nodulopustular skin lesions, bone pain, and constitutional symptoms . Evaluation revealed a disseminated infection with Mycobacterium chelonae subspecies chelonae, with cutaneous and osseous involvement documented by histopathologic studies and cultures . The bone involvement is a novel observation for this subspecies . The patient was successfully treated with a three-drug regimen of tobramycin sulfate, erythromycin stearate, and ciprofloxacin hydrochloride . We present a discussion of the case in the context of the literature.

Clin Pharmacol Ther, 1990 Aug, 48(2), 120 - 9
The erythromycin breath test as a predictor of cyclosporine blood levels; Watkins PB et al.; The daily dose of cyclosporine required to attain a desired blood level can vary greatly among patients . Because elimination of cyclosporine depends on its metabolism in the liver by an enzyme (cytochrome P-450IIIA) that also demethylates erythromycin, we reasoned that the ability of patients to demethylate a test dose of erythromycin might be useful in estimating their appropriate daily doses of cyclosporine . Accordingly, the {14C-N-methyl} erythromycin breath test was administered to 32 patients before they received 3.0, 5.0, or 7.5 mg/kg/day cyclosporine to treat psoriasis . We found that a simple mathematical equation incorporating just the 14CO2 production, the age of the patient, and the daily dose of cyclosporine accounted for almost 80% (R2 = 0.78) of the interpatient variability in cyclosporine blood levels we observed . Our data indicate that P-450IIIA activity largely accounts for the relationship between dose of cyclosporine and blood levels for an individual patient . We conclude that the erythromycin breath test may be a convenient guide for cyclosporine dosing.

Biochem Pharmacol, 1990 Jul 15, 40(2), 223 - 8
In vivo effects of erythromycin, oleandomycin and erythralosamine derivatives on hepatic cytochrome P-450; Delaforge M et al.; Rats have been treated with several derivatives of the erythromycin, erythralosamine or oleandomycin series, in order to compare their ability to induce cytochrome P-450 and to form stable 456 nm-absorbing cytochrome P-450 metabolite complexes . The data obtained confirm that the cytochromes P-450 induced in rats by various macrolides are similar to that induced by pregnenolone 16 alpha-carbonitrile: the cytochrome P-450 IIIA1 isozyme . It showed that: (i) formation of a stable inhibitory 456 nm-absorbing cytochrome P-450 complex is not a prerequisite for cytochrome P-450 induction but enhances induction by stabilization of the IIIA isozyme . Therefore, the best inducers lead also to the maximal in vivo amounts of cytochrome P-450 metabolite complex (except for 2'MBEM); (ii) affinity for cytochrome P-450 IIIA1 is not directly involved for induction; and (iii) hydrophobicity favors induction and formation of complexes . Structural factors are also involved.

J Clin Pharmacol, 1990 Jul, 30(7), 621 - 31
Gastrointestinal behavior of orally administered radiolabeled erythromycin pellets in man as determined by gamma scintigraphy; Digenis GA et al.; The behavior of single 250-mg doses of a multiparticulate form of erythromycin base (ERYC(R)), each including five pellets radiolabeled with neutron-activated samarium-153, was observed by gamma scintigraphy in seven male subjects under fasting and nonfasting conditions . The residence time and locus of radiolabeled pellets within regions of the gastrointestinal tract were determined and were correlated with plasma concentrations of erythromycin at coincident time points . Administration of food 30 minutes postdosing reduced fasting plasma erythromycin Cmax and area under the plasma erythromycin versus time curve (AUC) values by 43% and 54%, respectively . Mean peak plasma concentration of erythromycin (Cmax) in the fasting state was 1.64 micrograms/mL versus 0.94 micrograms/mL in the nonfasting state . Total oral bioavailability, as determined by mean AUC (0-infinity) of the plasma erythromycin concentration versus time curve, was 7.6 hr/micrograms/mL in the fasted state, versus 3.5 hr/micrograms/mL in the nonfasting state . Mean time to peak plasma erythromycin concentration (tmax) in the fasting state was 3.3 hours, versus 2.3 hours in the nonfasting state . Plasma concentrations of erythromycin in both fasting and nonfasting states were within acceptable therapeutic ranges . Evidence provided by this study: 1) indicates that pellet erosion and absorption of active erythromycin base begins when the enteric-coated pellets reach the highly vascular mucosa of the jejunum and proximal ileum, and is essentially completed within the ileum, with a significant portion absorbed in the medial-to-distal ileum; 2) confirms that acceptable therapeutic plasma levels of erythromycin are attained in nonfasting subjects (Cmax = 0.94 microgram/mL) and that superior plasma erythromycin concentrations (Cmax = 1.64 micrograms/mL) are achieved by administration of the dose on an empty stomach 1 to 2 hours before or after meals; 3) corroborates other comparative studies reporting greater fasting bioavailability with this multiparticulate dosage form of erythromycin base than with reference single tablet or particle-in-tablet formulations; and 4) indicates that neutron activation of stable isotopes incorporated as a normal excipient in industrially-produced formulations provides an effective means for in vivo evaluation of dosage forms through gamma scintigraphy.

Lijec Vjesn, 1990 Jul-Aug, 112(7-8), 216 - 21
{Clinical and epidemiologic features of acute respiratory infection caused by Mycoplasma pneumoniae}; Kuzman I et al.; The results of clinical and laboratory analysis and treatment, as well as epidemiological features of acute respiratory infections caused by Mycoplasma pneumoniae in 390 patients have been reported . The patients were treated at the University Hospital of Infectious Diseases "Dr . Fran Mihaljevic", Zagreb, between January 1, 1980, and December 31, 1985 . The diagnosis was established by the serologic method of complement fixation, on the grounds of fourfold increase or decrease of antibody titer in paired sera . Mycoplasma pneumoniae was the most frequently proved causative agent of acute respiratory infections in our admitted patients . There were 315 patients with pneumonia what makes 13.28% of all pneumonias, respectively 25.08% of nonbacterial pneumonias . Its participation in febrile respiratory catarrh syndrome was only 5.75% . Pneumonia occurred in schoolchildren most frequently, especially in those aged 10-14 years in whom 65.52% of nonbacterial pneumonias were connected with Mycoplasma pneumoniae . Men (230) were affected more frequently than women (160) . The main symptoms of pneumonia were temperature, headache and cough . Inflammatory infiltrates were mostly interstitial and located unilaterally in the lower lobes of the lungs . Pleural effusion was recorded in 24 patients (7.62%) . Doxycycline appeared to be the most effective antibiotic, but erythromycin and midecamycin yielded good results, as well.

Rev Infect Dis, 1990 Jul-Aug, 12 Suppl 6, S580 - 9
Treatment of chancroid, 1989; Schmid GP; Since recommendations for the treatment of chancroid were made in 1985, in vitro and in vivo data indicate that the two drugs recommended, erythromycin (500 mg four times a day for 7 days) and ceftriaxone (250 mg intramuscularly in a single dose), remain effective . The alternative therapies of trimethoprim-sulfamethoxazole (160/800 mg twice a day for 7 days) and amoxicillin-clavulanic acid (500/125 mg three times a day for 7 days) also appear to be effective, although there has been little experience with these drugs in the United States . Single-dose trimethoprim-sulfamethoxazole (640/3,200 mg) now lacks the efficacy of other regimens . The experience with ciprofloxacin (500 mg twice a day for 3 days) has been favorable, and other quinolones may prove useful . Concurrent infection with human immunodeficiency virus appears to result in an increased rate of failure of treatment for chancroid, and such cases may require more prolonged therapy.

J Fam Pract, 1990 Jul, 31(1), 62 - 4
Does patient education cause side effects? A controlled trial; Howland JS et al.; Ninety-eight adults treated with erythromycin for a variety of illnesses were randomized to two groups: the informed group received patient education about drug side effects, and the uninformed group were given no such information . Overall, 10% of the uniformed and 8% of the informed group felt the erythromycin bothered them in some way . There were no significant differences in the occurrence of various individual side effects . Compliance with therapy and the results of treatment were the same for both groups . In this study, informing patients about side effects of therapy did not have any detectable adverse effects.

Pediatr Dent, 1990 Jul-Aug, 12(4), 246 - 9
Epidermolysis bullosa--dental management and anesthetic considerations: case report; Lanier PA et al.; Epidermolysis bullosa represents a group of hereditary skin disorders manifested by an exceptional tendency of the skin and mucosa to form bullae and vesicles as a result of trauma or friction . Comprehensive dental care for precooperative-age children with this disorder frequently is managed in the operating room under a general anesthetic . This case report describes an anesthetic protocol for dental management which was effective and resulted in minimal postoperative trauma . Eucerin cream, Gauztex bandages, and DuoDerm pads were used to lubricate and stabilize anesthetic armamentarium . Preoperative and postoperative erythromycin antibiotic therapy was instituted to prevent infection of the bullae present . Early diagnosis and institution of preventive measures can minimize the need for restorative and surgical management in these children . However, when anesthetic management is necessary, the use of appropriate consultants and adjuncts can provide valuable support.

J Pediatr Gastroenterol Nutr, 1990 Jul, 11(1), 45 - 7
Intravenous erythromycin for postpyloric intubation; Di Lorenzo C et al.; Of 100 consecutive patients referred for antroduodenal manometry, we successfully intubated 89 with endoscopic and/or fluoroscopic guidance . In 8 of 8 patients who had failed with our usual techniques, we infused erythromycin 3 mg/kg i.v . over 1 h, and the tube moved through the pylorus and into the duodenum . Erythromycin, which stimulates propagation of 3 high amplitude antral contractions/min, appears to be a safe, noninvasive means to facilitate the postpyloric passage of tubes.

J Bacteriol, 1990 Jul, 172(7), 4008 - 16
Streptomyces relC mutants with an altered ribosomal protein ST-L11 and genetic analysis of a Streptomyces griseus relC mutant; Ochi K; Several relaxed (rel) mutants have been obtained from Streptomyces species by selecting colonies resistant to thiopeptin, an analogue of thiostrepton . Using two-dimensional gel electrophoresis, I compared the ribosomal proteins from rel and rel+ pairs of S . antibioticus, S . lavendulae, S . griseoflavus, and S . griseus . It was found that all of the Streptomyces rel mutants thus examined had an altered or missing ribosomal protein, designated tentatively ST-L11 . These rel mutants therefore could be classified as relC mutants and were highly sensitive to erythromycin or high temperature . A relC mutant of S . griseus was defective in streptomycin production, but phenotypic reversion of this defect to normal productivity was found at high incidence among progeny of the relC mutant . This phenotypic reversion did not accompany a reappearance of ribosomal protein ST-L11, and furthermore the ability of accumulating ppGpp still remained at a low level, thus suggesting existence of a mutation (named sup) which suppresses the streptomycin deficiency phenotype exhibited by the relC mutant . Genetic analysis revealed that there is a correlation between the rel mutation and the inability to produce streptomycin or aerial mycelia . The sup mutation was found to lie at a chromosomal locus distinct from that of the relC mutation . It was therefore concluded that the dependence of streptomycin production on the normal function of the relC gene could be entirely bypassed by a mutation at the suppressor locus (sup) . The suppressing effect of the sup mutation on the relC mutation was blocked when the afs mutation (defective in A-factor synthesis) was introduced into a relC sup double mutant . It is proposed that the sup gene or its product can be direct or indirect target for ppGpp.

Acta Gastroenterol Belg, 1990 Jul-Aug, 53(4), 446 - 57
The current status of gastric prokinetic drugs; Schapira M et al.; Several current gastrokinetic drugs (metoclopramide, domperidone, cisapride) are analysed in this review . After comparing the pharmacokinetics, the gastrointestinal prokinetic mechanisms and the side effects of each drug, their therapeutic uses are reviewed . All drugs improve symptoms of patients with gastro-oesophageal reflux disease, diabetic gastroparesis and idiopathic gastroparesis, but only cisapride seems capable to maintain a gastrokinetic effect under chronic administration . Erythromycin, which has a dramatic effect on hypomotility in diabetic gastroparesis, and opioid antagonists, may constitute new groups of efficient prokinetic drugs.

JAMA, 1990 Jun 20, 263(23), 3160 - 3
Improved pregnancy outcome following successful treatment of chlamydial infection; Cohen I et al.; Pregnancy outcomes of 244 women, successfully treated with erythromycin ethylsuccinate for cervical chlamydial infection, were compared with those of 79 chlamydia-positive pregnant women, who failed to respond to treatment, and 244 chlamydia-free control women, who were not treated . The three groups were at high risk for infection with Chlamydia trachomatis . The frequencies of premature rupture of the membranes, premature contractions, and small-for-gestational-age infants were significantly lower in the successfully treated patients when compared with those of the chlamydia-positive patients, but were not significantly different when compared with those of the control patients . These data indicate that in a pregnant population at high risk for infection with C trachomatis, repeated prenatal chlamydial testing, plus successful erythromycin treatment, can significantly reduce certain adverse effects on pregnancy outcome.

Biochem J, 1990 Jun 15, 268(3), 765 - 9
Induction of cytochrome P450III and P450IV family proteins in streptozotocin-induced diabetes; Barnett CR et al.; The effect of insulin-dependent diabetes on the hepatic microsomal activity of cytochrome P450III and P450IV family proteins was investigated in rats pretreated with streptozotocin . In order to discern between the effects of the diabetogen per se and those of the ensuing diabetes, streptozotocin-treated rats received in addition either nicotinamide to prevent the onset of diabetes or daily treatment with insulin to antagonize the effects of diabetes . Streptozotocin-treated rats displayed higher ethylmorphine and erythromycin N-demethylase activities and lauric acid hydroxylase activity . Increases were also detected immunologically by using monospecific polyclonal antibodies against the P450III and P450IV families . All effects were prevented by nicotinamide and effectively antagonized by insulin . In order to evaluate the role of the ketone bodies in the diabetes-induced increases in the above activities, rats were rendered hyperketonaemic by dietary administration of medium-chain triacylglycerols . These hyperketonaemic animals displayed high laurate hydroxylase activity and P450IV apoprotein levels, similar to those seen in the diabetic animals . Hyperketonaemia induced by dietary means caused a modest increase in the demethylation of erythromycin and had no significant effect on the N-demethylation of ethylmorphine . Furthermore, no marked increases were evident in the P450III apoprotein levels in the hyperketonaemic animals . It is concluded that insulin-dependent diabetes induces proteins of the P450III and P450IV families, and that the hyperketonaemia that accompanies diabetes is largely responsible for the changes in the latter family.

Ir Med J, 1990 Jun, 83(2), 70 - 1
Management of tonsillitis by the general practitioner; Timon CI et al.; Seventy-eight of 107 general practitioners completed a questionnaire to assess the management of recurrent acute tonsillitis by the primary care physician . Penicillin was the antibiotic of choice in acute tonsillitis, used by 74 (95%) respondents . Of these, 45% recommended ampicillin/amoxycillin . In the case of penicillin allergy, 67 (86%) chose erythromycin . For the treatment of tonsillitis unresponsive to initial therapy, a wide variety of agents were quoted; the most common being erythromycin (27 cases, 35%) and co-trimoxazole (16 cases, 20%) . There were 17 separate indications for surgical referral given, the most common being recurrent tonsillitis (68 cases, 87%) . Two or more reasons for surgical referral were stated by 55 (71%) GPs . These findings are discussed with particular reference to recent reports of penicillinase producing bacteria in association with recurrent acute tonsillitis.

Pneumologie, 1990 Jun, 44(6), 826 - 8
{Ciprofloxacin in the treatment of Legionnaires' disease}; Zabel L et al.; Case report on a granulocytopenic patient suffering from acute myeloid leukaemia and legionnaire's disease as a complication . Under therapy with ciprofloxacin (2 x 200 mg/die) the symptoms decreased within five days; hence, ciprofloxacin seems to be a good alternative to erythromycin and rifampicin in the therapy of legionnaire's disease in immunodeficient patients.

Clin Pharmacol Ther, 1990 Jun, 47(6), 694 - 7
Pharmacokinetic evaluation of erythromycin and caffeine administered with bromocriptine; Nelson MV et al.; A study was performed to determine if the pharmacokinetics of bromocriptine is altered by factors that have been shown to interact with other ergot compounds . The effects on bromocriptine plasma concentrations by bromocriptine coadministration with caffeine and erythromycin were evaluated in five male volunteers . Serial blood samples were obtained during a 12-hour period after a single 5 mg oral dose of bromocriptine (alone and after 4-day treatments of either erythromycin estolate, 250 mg four times/day, or caffeine, 200 mg four times/day) . There were no significant alterations of bromocriptine pharmacokinetic parameters after caffeine, although statistical power was very low . With the use of erythromycin, the bromocriptine area under the concentration-time curve standardized to body weight increased significantly by 268%, whereas peak bromocriptine plasma concentration (Cmax) increased to 4.6 times the Cmax from bromocriptine alone . Time to achieve Cmax was not altered by erythromycin . We conclude that erythromycin can markedly increase the systemic bioavailability of bromocriptine, which can lead to increased therapeutic or adverse effects, whereas the effects of caffeine require further study.

Ann Otol Rhinol Laryngol, 1990 Jun, 99(6 Pt 1), 445 - 50
Otolaryngologic management of posttransplant lymphoproliferative disease in children; Sculerati N et al.; Twelve of 14 children (86%) given a pathologic diagnosis of posttransplantation lymphoproliferative disease (PTLD) at the Children's Hospital of Pittsburgh presented with head and neck symptoms, and are included in this retrospective analysis . Upper airway obstruction was the most common symptom, evident in nine children (75%) . Ten children (83%) had febrile illnesses with dysphagia, odynophagia, and evidence of hypertrophy of components of Waldeyer's ring . Associated findings included cervical adenopathy, sinusitis, and otitis media . The two remaining children had an intratracheal and paratracheal mass, respectively . Excision of obstructing lymphoid tissue with proper handling of the specimen is advocated for diagnosis and relief of airway obstruction . Systemic therapy is necessary for treatment of PTLD and includes reduction of immunosuppression . Erythromycin causes elevation in cyclosporine levels and should be avoided in patients taking this drug.

Acta Paediatr Jpn, 1990 Jun, 32(3), 315 - 8
Intrauterine Chlamydia trachomatis infection in a premature infant; Niwa A et al.; Intrauterine Chlamydia trachomatis infection was strongly suspected in a premature infant born in the 32nd week of gestation . The membranes were artificially ruptured at the time of delivery . This infant showed a high titer of specific IgM antibody to Chlamydia trachomatis at one hour after birth . He showed mild respiratory distress and was treated with oral erythromycin for three weeks . He was discharged home at the age of 46 days.

J Antimicrob Chemother, 1990 Jun, 25(6), 975 - 84
Comparative efficacy and tolerance of erythromycin and josamycin in the prevention of bacteraemia following dental extraction; Sefton AM et al.; The tolerance and pharmacokinetics of erythromycin stearate and josamycin base were compared in healthy dental students . The efficacy and tolerance of the two antibiotics were compared in the prevention of bacteraemia following dental extraction . Erythromycin achieved higher serum levels at the time of extraction in dental patients than did josamycin . Erythromycin was rapidly and better absorbed than josamycin in the student volunteers, but josamycin caused less gastrointestinal side effects than erythromycin . Both antibiotics were only marginally more effective than placebo in preventing bacteraemia following dental extraction.

J Infect Dis, 1990 Jun, 161(6), 1296 - 8
Pertussis in an adult man infected with the human immunodeficiency virus; Doebbeling BN et al.; A 25-year-old man infected with the human immunodeficiency virus (HIV) presented with paroxysmal cough and dyspnea of 4-months duration . An extensive evaluation including bronchoscopy was negative . A nasopharyngeal swab was positive by direct fluorescent antigen detection and culture for Bordetella pertussis . Respiratory isolation, treatment with erythromycin, and prophylaxis of household contacts was used to eradicate the organism and prevent transmission . Pertussis should be considered as a cause of prolonged cough and dyspnea in patients with HIV infection . The course of this patient was consistent with the concept that cell-mediated immunity is necessary for elimination of B . pertussis.

Arzneimittelforschung, 1990 Jun, 40(6), 686 - 9
Mechanism of azithromycin uptake in human polymorphonuclear leucocytes; Laufen H et al.; The new antibiotic azithromycin (CP-62.993) is enriched in human polymorphonuclear leucocytes by up to 300-fold the extra-cellular concentrations . To approach an understanding of the underlying mechanism of this unique behavior of azithromycin, some characteristics of the uptake process were investigated in vitro . The speed of the uptake in human polymorphonuclear leucocytes was found to be independent of the extracellular starting concentrations of azithromycin . There was no indication of saturation up to extracellular concentrations of 100 micrograms/ml . The uptake was largely determined by incubation temperatures . At 4 degrees C no penetration into the cells could be observed . The activation energy of azithromycin uptake came to 144 kJ mol-1, twice the value of erythromycin uptake . The presence of various inhibitors of cell metabolism did not change the intracellular accumulation compared to control, nor did the presence of some agents which interfere with certain transport channels . These findings suggest that passive diffusion is an essential mechanism of azithromycin transport through the phagocyte membrane, while active transport is less important . The high cellular enrichment of azithromycin and the relatively high activation energy of the uptake process could be explained by accumulation of the drug in phagocytic lysosomes and this would also be in keeping with pH partition considerations.

Antimicrob Agents Chemother, 1990 Jun, 34(6), 1056 - 60
Intracellular accumulation of azithromycin by cultured human fibroblasts; Gladue RP et al.; Azithromycin was shown to achieve high concentrations in human skin fibroblasts . Intracellular penetration occurred rapidly (10 micrograms/mg of cellular protein after 3 h) and then increased progressively over a 3-day period; azithromycin accumulated up to 21 times more than erythromycin (61.1 versus 2.9 micrograms/mg of protein) . Uptake was dependent on the extracellular concentration, was inhibited at 4 degrees C, did not occur in nonviable cells, and was reduced by a low pH . Intracellular accumulation was not affected by the metabolic inhibitor 2,4-dinitrophenol or sodium fluoride or by the nucleoside transport inhibitor 2-chloradenosine . Once concentrated in cells, azithromycin remained intracellular and was released slowly in the absence of extracellular drug, compared with erythromycin (17 versus 78% released after 1 h) . After 48 h of incubation in drug-free medium, 27% of the initial amount of azithromycin remained cell associated . The release of azithromycin was not affected by various monokines reported to stimulate fibroblasts (interleukin-1 or tumor necrosis factor) or by exposure to bacteria . Incubation of azithromycin-loaded fibroblasts with human polymorphonuclear leukocytes resulted in a higher intracellular accumulation of azithromycin in polymorphonuclear leukocytes than in cells incubated with free nonintracellular azithromycin for the same time (8.3 versus 2.2 micrograms/ml after 2 h), suggesting a more efficient or rapid uptake through cell-to-cell interaction . The widespread distribution of fibroblasts in tissues suggests a potential for these cells, and possibly other lysosome-containing tissue cells, to serve as a reservoir for azithromycin, slowly releasing it for activity against extracellular organisms at sites of infection and passing it to phagocytes for activity against intracellular pathogens and potential transport to sites of infection.

Control Clin Trials, 1990 Jun, 11(3), 187 - 98
Value of a run-in period in a drug trial during pregnancy; Blackwelder WC et al.; The Vaginal Infections and Prematurity (VIP) Study included a clinical trial of the efficacy of erythromycin in preventing adverse pregnancy outcomes . A prerandomization run-in period was part of the trial design . During this period, women were given 1 week's supply of placebo pills to test their compliance . Those who met certain criteria for compliance, were otherwise still eligible, and agreed to participate were then randomized to receive erythromycin or placebo for a maximum of 10 weeks . During 2 years of the VIP Study, 1476 (71%) of 2071 women who began the run-in period were randomized . Women at least 30 years of age, those not smoking during pregnancy or shortly before pregnancy, and those still working outside the home at the time of enrollment were more likely than other women to be randomized after the run-in . Calculations of relative efficiency, based on a standard sample-size formula, suggest that the VIP run-in procedure not only eliminated potentially noncompliant women before randomization but also increased the power of the trial . Similar calculations which incorporated costs suggest that the run-in also resulted in lower costs, compared to a trial with equivalent power but no run-in period.

Ann Otol Rhinol Laryngol Suppl, 1990 Jun, 148, 39 - 41
Clinical perspectives on ototoxic drugs; Matz GJ; Ototoxic drugs such as salicylates, the aminoglycoside antibiotics, loop diuretics, cisplatin, erythromycin, and vancomycin are widely used in clinical practice . The most commonly used are aspirin and the aminoglycoside antibiotics . This chapter briefly discusses the pharmacology of the commonly prescribed ototoxic drugs and the doses that may result in ototoxicity . An outline for the monitoring of ototoxic drugs is presented . The role of topical ear drops as a possible cause of ototoxicity is reviewed.

Gene, 1990 May 31, 90(1), 21 - 9
Cloning of genes involved in erythromycin biosynthesis from Saccharopolyspora erythraea using a novel actinomycete-Escherichia coli cosmid; Tuan JS et al.; Two plasmids were constructed that replicate in Saccharopolyspora (Sac.) erythraea, Escherichia coli and Streptomyces (S.) lividans, and used for the cloning of a locus involved in the synthesis of the macrolide antibiotic erythromycin (Er) . Plasmid pAL7002 contains the thiostrepton-resistance gene (tsr), a replicon-containing fragment from pJVI and pUC9 . Plasmid pNJI contains the lambda cos site but is otherwise similar to pAL7002 . A library of total DNA from Sac . erythraea was constructed in pNJI and probed in colony hybridizations with a DNA fragment containing ermE, the Sac . erythraea ErR-encoding gene . Plasmids obtained were subsequently introduced into EryA mutants of Sac . erythraea blocked in synthesis of Er (Ery-) and transformants were screened for restoration of Er production (Ery+) . Several plasmids were found to convert two mutants to Ery+, but a third EryA strain could not be restored to Ery+ by any of the plasmids employed . A 5-kb segment, designated eryAI, responsible for restoring the Ery+ phenotype in the EryA strains, was identified and mapped in the segment 12 to 17 kb downstream from ermE . Gene disruption experiments indicated that the 5-kb length of eryAI is fully internal to an eryAI-containing transcript . In Southern blots it was shown that one of the EryA strains carried a small deletion in eryAI and that, in at least some of the transformants restored to Ery+, the deletion had been replaced by the wild-type eryAI allele.(ABSTRACT TRUNCATED AT 250 WORDS)

J Biol Chem, 1990 May 15, 265(14), 7894 - 9
Identification of a rRNA/chloramphenicol interaction site within the peptidyltransferase center of the 50 S subunit of the Escherichia coli ribosome; Marconi RT et al.; We have used oligodeoxyribonucleotide probes to investigate possible interactions between chloramphenicol and portions of the rRNA contained within the peptidyltransferase center of the Escherichia coli ribosome . Oligodeoxyribonucleotide probes complementary to bases 2448-2454, 2468-2482, and 2497-2505 of 23 S rRNA were hybridized to 50 S subunits in situ . Probe binding was qualitatively assessed by sucrose gradient centrifugation . Each probe was shown to bind specifically with its intended binding site through digestion of the rRNA within the RNA/DNA hetero-duplexes with RNase H and analysis of the digestion fragments using gel electrophoresis . Competitive binding experiments were conducted between each probe and the antibiotics chloramphenicol and erythromycin . The binding of a probe complementary to bases 2497-2505 was attenuated by 70% upon the binding of chloramphenicol . A probe complementary to bases 2468-2482 showed an increase in binding of 14% while binding of a probe complementary to bases 2448-2454 was not affected by chloramphenicol binding . Erythromycin did not affect the binding of any of these probes to 50 S subunits . These results suggest that bases within the 2497-2505 region of 23 S rRNA in E . coli may be involved in a chloramphenicol/rRNA interaction.

Peptides, 1990 May-Jun, 11(3), 515 - 9
The erythromycin derivative EM-523 is a potent motilin agonist in man and in rabbit; Depoortere I et al.; Erythromycin may stimulate gastrointestinal motor activity via its effect upon motilin receptors . We have studied the ability of the derivative EM-523 {de(N-methyl)-N-ethyl-8,9-anhydroerythromycin A 6,9-hemiacetal} to induce contractions in duodenal smooth muscle strips and to displace labeled motilin bound to antral smooth muscle, in man and in rabbit . In both species EM-523 approached the potency of motilin for inducing contractions . Thus pED50 values were 7.84 +/- 0.11 and 8.69 +/- 0.12 for motilin in, respectively, man and rabbit, against 6.08 +/- 0.13 and 8.19 +/- 0.10 for EM-523 . In rabbit the efficacy of both compounds decreased in parallel aborally, the responses to EM-523 could not be blocked by atropine (10(-7) M) or TTX (10(-7) M), and both compounds were unable to further enhance the maximum effect to the other compound . In binding studies the order of potency was the same as in the contraction studies . The pIC50 values were: motilin (8.84 +/- 0.31, 9.17 +/- 0.20) greater than EM-523 (7.89 +/- 0.1, 8.40 +/- 0.10) . A Schild plot revealed that EM-523 was a competitive inhibitor of motilin receptor binding in man and in rabbit . We conclude that EM-523 is a potent motilin agonist.

J Toxicol Environ Health, 1990 May, 30(1), 33 - 52
Comparison of polychlorinated dibenzodioxin levels with hepatic mixed-function oxidase induction in great blue herons; Bellward GD et al.; As part of the Canadian Wildlife Service monitoring of great blue herons in British Columbia, eggs were collected from three colonies with low, intermediate, and high levels of PCDD and PCDF contamination: Nicomekl, Vancouver, and Crofton, respectively . One egg from each nest was used for chemical analysis by GC-MS; the others were hatched . Liver microsomes were prepared from the heron chicks and used for determination of cytochrome P-450-dependent activities . No erythromycin N-demethylase activity was found in any sample . Ethoxyresorufin O-dealkylase activity in the Nicomekl group was similar to that in pigeons, a control altricial species . The ethoxyresorufin activity in the herons from the Crofton colony was 2.6-fold higher than in the Nicomekl group . The Vancouver colony was intermediate . No difference among the three heron colonies was found in pentoxyresorufin O-dealkylase activity, although levels were 20-33 times that in the pigeon . Chemical analysis was carried out on paired heron eggs . Vancouver and Crofton eggs contained 13.5 and 21 times the levels of 2,3,7,8-TCDD compared to the Nicomekl group . The Crofton eggs contained higher levels of several other contaminants also . A highly significant correlation (p less than .001) was found between ethoxyresorufin O-dealkylase and 2,3,7,8-TCDD concentrations . The correlation coefficient did not change when ethoxyresorufin O-dealkylase was compared to total chemical contamination using several toxic equivalency factors . Multiple regression analysis resulted in only one predictor variable for ethoxyresorufin O-dealkylase: 2,3,7,8-TCDD.

J Infect, 1990 May, 20(3), 227 - 9
Legionnaires' disease due to Legionella anisa; Fallon RJ et al.; The first case of Legionnaires' disease due to Legionella anisa is described . The patient, a 31-year-old man, made a rapid and complete recovery when treated with erythromycin.

Obstet Gynecol, 1990 May, 75(5), 752 - 6
Amoxicillin therapy for Chlamydia trachomatis in pregnancy; Crombleholme WR et al.; For treating Chlamydia trachomatis cervical infection in pregnancy, the Centers for Disease Control guidelines recommend either erythromycin base or erythromycin ethylsuccinate . There is no alternate therapy . Because of compliance problems with erythromycin regimens due to gastrointestinal side effects, such an alternative is needed . For this reason, we compared, in an open trial, the efficacy and patient compliance of amoxicillin (500 mg three times a day for 7 days) with those of erythromycin base (500 mg four times a day for 7 days) in treating C trachomatis cervical infections during pregnancy . In the amoxicillin group, 63 of 64 women (98.4%) had negative cervical cultures after treatment, compared with 55 of 58 women (94.8%) treated with erythromycin base . Vertical transmission to the infants was assessed by culture and/or persistent or rising immunoglobulin G antichlamydial antibody . In the amoxicillin group, 37 of 39 infants (94.9%) had no evidence of chlamydial infection, compared with 32 of 36 infants (88.8%) in the erythromycin group . These differences were not significant . The frequency of side effects was higher with erythromycin base than with amoxicillin (15 versus 8%), although not significantly so . However, the frequency of stopping medication because of side effects was significantly higher with erythromycin base than with amoxicillin (13 versus 2%; P less than .006) . These results suggest that amoxicillin may be an acceptable alternative treatment for chlamydial infections in pregnancy.

Oral Surg Oral Med Oral Pathol, 1990 May, 69(5), 619 - 30
A comparison of erythromycin and cefadroxil in the prevention of flare-ups from asymptomatic teeth with pulpal necrosis and associated periapical pathosis; Morse DR et al.; In a previous study by our group with patients having asymptomatic teeth with pulpal necrosis and an associated periapical radiolucent lesion (PN/PL), it was shown that prophylactic administration of penicillin V or erythromycin (high-dose, 1-day regimen) resulted in a low incidence of flare-up (mean = 2.2%) and a low incidence of swelling and pain not associated with flare-up . No hypersensitivity responses occurred, and gastrointestinal side effects were found primarily with the erythromycins . To ascertain whether a single-dose administration of a long-acting 1-gm tablet of the cephalosporin antibiotic cefadroxil would result in a similar outcome, the present study was undertaken with 200 patients having quiescent PN/PL . The patients were randomly given either cefadroxil or erythromycin (base or stearate) . Evaluations of flare-up were done 1 day, 1 week, and 2 months after endodontic treatment . A 2.0% flare-up incidence was found, with no statistically significant differences for cefadroxil (1.0%), stearate (2.0%), or base (4.0%) . No hypersensitivity responses occurred . Gastrointestinal side effects were found primarily with the erythromycins (19.0%) . The results showed that a 1-gm, single-dose regimen of cefadroxil was as effective as erythromycin and penicillin in preventing flare-ups and serious sequelae . A comparative analysis of the data from our first study (no peritreatment antibiotics) and the pooled data from our last three investigations (including the current trial) showed that peritreatment antibiotic coverage significantly reduced flare-ups and serious sequelae after endodontic treatment of asymptomatic PN/PL (p less than 0.001).

J Bacteriol, 1990 May, 172(5), 2541 - 6
Mutation and cloning of eryG, the structural gene for erythromycin O-methyltransferase from Saccharopolyspora erythraea, and expression of eryG in Escherichia coli; Paulus TJ et al.; A mutant strain derived by chemical mutagenesis of Saccharopolyspora erythraea (formerly known as Streptomyces erythreus) was isolated that accumulated erythromycin C and, to a lesser extent, its precursor, erythromycin D, with little or no production of erythromycin A or erythromycin B (the 3"-O-methylation products of erythromycin C and D, respectively) . This mutant lacked detectable erythromycin O-methyltransferase activity with erythromycin C, erythromycin D, or the analogs 2-norerythromycin C and 2-norerythromycin D as substrates . A 4.5-kilobase DNA fragment from S . erythraea originating approximately 5 kilobases from the erythromycin resistance gene ermE was identified that regenerated the parental phenotype and restored erythromycin O-methyltransferase activity when transformed into the erythromycin O-methyltransferase-negative mutant . Erythromycin O-methyltransferase activity was detected when the 4.5-kilobase fragment was fused to the lacZ promoter and introduced into Escherichia coli . The activity was dependent on the orientation of the DNA relative to lacZ . We have designated this genotype eryG in agreement with Weber et al . (J.M . Weber, B . Schoner, and R . Losick, Gene 75:235-241, 1989) . It thus appears that a single enzyme catalyzes all of the 3"-O-methylation reactions of the erythromycin biosynthetic pathway in S . erythraea and that eryG codes for the structural gene of this enzyme.

J Bacteriol, 1990 May, 172(5), 2372 - 83
Organization of a cluster of erythromycin genes in Saccharopolyspora erythraea; Weber JM et al.; We used a series of gene disruptions and gene replacements to mutagenically characterize 30 kilobases of DNA in the erythromycin resistance gene (ermE) region of the Saccharopolyspora erythraea chromosome . Five previously undiscovered loci involved in the biosynthesis of erythromycin were found, eryBI, eryBII, eryCI, eryCII, and eryH; and three known loci, eryAI, eryG, and ermE, were further characterized . The new Ery phenotype, EryH, was marked by (i) the accumulation of the intermediate 6-deoxyerythronolide B (DEB), suggesting a defect in the operation of the C-6 hydroxylase system, and (ii) a block in the synthesis or addition reactions for the first sugar group . Analyses of ermE mutants indicated that ermE is the only gene required for resistance to erythromycin, and that it is not required for production of the intermediate erythronolide B (EB) or for conversion of the intermediate 3-alpha-mycarosyl erythronolide B (MEB) to erythromycin . Mutations in the eryB and eryC loci were similar to previously reported chemically induced eryB and eryC mutations blocking synthesis or attachment of the two erythromycin sugar groups . Insertion mutations in eryAI, the macrolactone synthetase, defined the largest (at least 9-kilobase) transcription unit of the cluster . These mutants help to define the physical organization of the erythromycin gene cluster, and the eryH mutants provide a source for the production of the intermediate DEB.

Enferm Infecc Microbiol Clin, 1990 May, 8(5), 278 - 81
{Childhood legionellosis}; Ferrer A et al.; Four cases of hospital acquired pneumonia are reported in children aged from 10 days to 7 years, in whom L . pneumophila serogroup 6 was isolated . All patients were sporadic cases occurring during a two year period (1987-1988) in the Pediatric Hospital of our institution . L . pneumophila was isolated in samples of pleural fluid, lung biopsy, tracheal aspirate, bronchial brushing and bronchoalveolar lavage . All our patients were immunologically depressed and three died . Only in two cases of erythromycin therapy was administered, as the etiology of their pneumonia was not suspected . The literature on other reported cases of infantile legionellosis is discussed.

N Engl J Med, 1990 Apr 12, 322(15), 1028 - 31
Improvement of gastric emptying in diabetic gastroparesis by erythromycin . Preliminary studies; Janssens J et al.; Erythromycin mimics the effect of the gastrointestinal polypeptide motilin on gastrointestinal motility, probably by binding to motilin receptors and acting as a motilin agonist . Erythromycin may thus have clinical application in patients with disturbances of gastroduodenal motility, such as diabetic gastroparesis . To examine this possibility, we studied the effect of erythromycin on gastric emptying in 10 patients with insulin-dependent diabetes mellitus and gastroparesis . We studied the emptying of liquids and solids simultaneously on separate days after the intravenous administration of erythromycin (200 mg) or placebo, using a double-isotope technique and a double-blind, crossover design . Erythromycin shortened the prolonged gastric-emptying times for both liquids and solids to normal . For example, 120 minutes after the ingestion of a solid meal, mean (+/- SE) retention was 63 +/- 9 percent with placebo and 4 +/- 1 percent with erythromycin, as compared with 9 +/- 3 percent in 10 healthy subjects . The corresponding values 120 minutes after the ingestion of a liquid meal were 32 +/- 4, 9 +/- 3, and 4 +/- 1 percent, respectively . Gastric emptying also improved, but to a lesser degree, in the 10 patients after four weeks of treatment with oral erythromycin (250 mg three times a day) . These preliminary results suggest that erythromycin may have therapeutic value in patients with severe diabetic gastroparesis.

Rinsho Ketsueki, 1990 Apr, 31(4), 502 - 5
{Long-term surviving child with acute lymphoblastic leukemia complicated with legionellosis}; Tanabe N et al.; An 11 year-old girl was diagnosed as acute lymphoblastic leukemia (ALL) on November 26th 1979 and was induced into complete remission with vincristine and prednisolon . After consolidation therapy with daunomycin, vincristine and prednisolone, she developed pneumonia on January 21st 1980 . No cause of pneumonia was found by sputum culture or serologic tests . Treatment with cefmetazol (CMZ), sulbenicillin (SBPC) and minocycline (MINO) was not effective but 9 g/day of LCM made a remarkable effect . Indirect immunofluorescence assay of antibody showed x 512 titers on January 22nd and in her recovery period, the titers showed eight times increased up to x 4,000 . The diagnosis of Legionellosis was made on CDC's criteria . She recovered completely with sequential lincomycin (LCM) and erythromycin (EM) therapy . On October 1989, she is still in the first complete remission of ALL for more than 8 years.

Antimicrob Agents Chemother, 1990 Apr, 34(4), 594 - 9
In vitro effect of fluoroquinolones on theophylline metabolism in human liver microsomes; Sarkar M et al.; Some quinolone antibiotics cause increases in levels of theophylline in plasma that lead to serious adverse effects . We investigated the mechanism of this interaction by developing an in vitro system of human liver microsomes . Theophylline (1,3-dimethylxanthine) was incubated with human liver microsomes in the presence of enoxacin, ciprofloxacin, norfloxacin, or ofloxacin . Theophylline, its demethylated metabolites (3-methylxanthine and 1-methylxanthine), and its hydroxylated metabolite (1,3-dimethyluric acid) were measured by high-pressure liquid chromatography, and Km and Vmax values were estimated . Enoxacin and ciprofloxacin selectively blocked the two N demethylations; they significantly inhibited the hydroxylation only at high concentrations . Norfloxacin and ofloxacin caused little or no inhibition of the three metabolites at comparable concentrations . The extent of inhibition was reproducible in five different human livers . Inhibition enzyme kinetics revealed that enoxacin caused competitive and mixed competitive types of inhibition . The oxo metabolite of enoxacin caused little inhibition of theophylline metabolism and was much less potent than the parent compound . Nonspecific inhibition of cytochrome P-450 was ruled out since erythromycin N demethylation (cytochrome P-450 mediated) was unaffected in the presence of enoxacin . These in vitro data correlate with the clinical interaction described for these quinolones and theophylline . We conclude that some quinolones are potent and selective inhibitors of specific isozymes of human cytochrome P-450 that are responsible for theophylline metabolism . This in vitro system may be useful as a model to screen similar compounds for early identification of potential drug interactions.

J Pharmacol Exp Ther, 1990 Apr, 253(1), 387 - 94
Cytochrome P 450 isoenzymes, epoxide hydrolase and glutathione transferases in rat and human hepatic and extrahepatic tissues; de Waziers I et al.; The organ distribution of microsomal cytochrome P 450 isoenzymes (P 450), microsomal epoxide hydrolase (EH) and cytosolic glutathione-S-transferases was investigated by immunoblotting and enzyme measurements in rats and humans . In rats, P 450 IA1 was detected only in the duodenum, and P 450 IA2 and IIC11 were detected only in the liver . The highest concentrations of P 450 IIB1/B2 were found in the lung and in the duodenum; pentoxyresorufin-O-dealkylase activity was closely correlated with the amounts of P 450 IIB1/B2 in the different organs . P 450 IIE1 was present in liver, kidney and lung, whereas EH was found in liver, intestine and kidney . In humans, P 450 IIIA4 was detected in all tissues investigated; the highest concentrations were found in liver and intestine . The P 450 IIIA4 level was closely correlated with that of erythromycin demethylase and pentoxyresorufin-O-dealkylase activities . P 450 IIC8-10, IIE1 and IID6 were expressed in liver and intestine, P 450 9 in liver and kidney and P 450 IA2 in liver . EH was identified only in liver, intestine and kidney . In both species, concentrations and total amounts of P 450 isoenzymes and EH were much lower in all extrahepatic tissues than in the liver . Conversely, glutathione-S-transferase-pi was abundant in human intestine and colon compared to liver . Glutathione-S-transferase-mu polymorphism was confirmed in all tissues investigated . This extensive study showed that the pattern of (iso) enzymes was different in all tissues studied; consequently, xenobiotic metabolism would appear to be very different in each type of tissue.

J Reprod Med, 1990 Apr, 35(4), 362 - 7
Treatment of Chlamydia trachomatis identified with Chlamydiazyme during pregnancy . Impact on perinatal complications and infants; Black-Payne C et al.; A rapid enzyme immunoassay antigen detection system (Chlamydiazyme) was used to screen 199 asymptomatic, third-trimester women . Fifty-two (26%) were Chlamydiazyme positive; they were mostly primiparous, single, young and black . Infected women were offered erythromycin therapy, counseling and posttherapy retesting . Sexual partners were treated likewise . Erythromycin compliance, determined by a questionnaire, was high (92%), and side effects (16%) were tolerable . Pregnancy outcome and infant illnesses were monitored to determine the effectiveness of therapy . There were no significant differences in pregnancy outcome in the Chlamydiazyme-negative and treated, Chlamydiazyme-positive women . Prospective evaluation of infants born to 48 negative and 50 treated, Chlamydiazyme-positive women revealed no significant differences in the incidence of respiratory tract illnesses or conjunctivitis . Chlamydiazyme can be used in a screening program to identify and treat third-trimester women infected with C trachomatis . As previously reported, erythromycin therapy for colonized women interrupted the expected transmission of C trachomatis to their infants.

Genitourin Med, 1990 Apr, 66(2), 105 - 7
Sulphaphenazole, streptomycin and sulphaphenazole combination, trimethoprim, and erythromycin in the treatment of chancroid; Kumar B et al.; One hundred and thirty six patients with chancroid were treated with four different treatment regimens; (A) Sulphaphenazole 1 g 12 hourly by mouth x 10 days (B) Inj streptomycin 1 g intramuscularly daily with sulphaphenazole 1 g 12 hourly orally x 10 days; (C) trimethoprim 200 mg 12 hourly by mouth x 7-10 days, and (D) erythromycin 500 mg 6 hourly orally x 7-10 days . Cure rates of 9% with sulphaphenazole alone, 48% with streptomycin and sulphaphenazole combination, 93% with trimethoprim and 100% with erythromycin were obtained . Sulphaphenazole alone or in combination with streptomycin were thus inferior in the treatment of chancroid . There is need for modification of treatment regimens recommended for chancroid in the textbooks of dermatology and venereology . Trimethoprim can be recommended as first line of treatment for chancroid in developing countries like India where resistance to trimethoprim is uncommon and erythromycin is suggested as a second line of therapy because by that time syphilis can be easily ruled out.

J Infect Dis, 1990 Apr, 161(4), 618 - 25
A new respiratory tract pathogen: Chlamydia pneumoniae strain TWAR; Grayston JT et al.; Chlamydia pneumoniae strain TWAR, the new third species of Chlamydia, is a common cause of pneumonia and other acute respiratory tract infections . About 10% of hospitalized and outpatient pneumonia cases have been associated with TWAR infection . TWAR is among the four or five most commonly identified causes of all pneumonia . Most TWAR infections are mild or asymptomatic, but occasionally severe pneumonia with death has been observed . Laboratory diagnosis is not generally available . Vigorous treatment with tetracycline or erythromycin is recommended . Both epidemic and endemic infections have been described in North America and the Nordic Countries . Population prevalence antibody studies suggest that TWAR infection is wide-spread throughout the world, that nearly everyone is infected and reinfected during their life-time, and that infection is common in all ages except those less than 5 years in temperate zone countries . The infection is transmitted from person to person, apparently with a long incubation period.

Acta Virol, 1990 Apr, 34(2), 171 - 7
Properties in culture and persistence in cotton rats of the Rickettsia prowazekii vaccine strain E and its mutants; Ignatovich VF et al.; Cultural properties and the capacity for persistence were studied in spontaneous erythromycin-resistant (E errSM), in induced erythromycin-resistant (E errI) mutants and in a virulent revertant (E Vir) of the vaccine strain E, as compared with parent vaccine strain E and standard virulent strain Breinl of Rickettsia prowazekii . Cultural properties of the strains were found to differ in passages in chick embryos (CE) and cultures of FL cells . Multiplication indices in CE of mutant E errI were significantly lower than those of other strains (E, E errSM, E Vir, Breinl) . The multiplication rate in FL cells was found to be high in strains E errSM, Breinl, E Vir, being much lower in strains E errI and E . The capacity of the virulent revertant E Vir to persist in cotton rat (CR) was higher as compared with that of standard strain Breinl and significantly higher than that of the parent strain E . Low level carrier state of rickettsia was registered in CR infected with the mutant E errI.

J Laryngol Otol, 1990 Mar, 104(3), 200 - 2
Otitis media with effusion: can erythromycin reduce the need for ventilating tubes?
Moller P, Dingsor G.
Otitis media with effusion (OME) is a common condition among children and is characterized by nonpurulent fluid in the middle ear and fluctuating conductive hearing loss . Most children will spontaneously regain normal air-filled middle ears, but a certain number will have persistent problems . In our department we will treat annually about 500 children on an outpatient basis, with the insertion of ventilating tubes in the eardrum . The reason for this study was to evaluate the effect of erythromycin, instead of inserting a ventilation tube, in children with bilateral OME of longer duration than three months (double blind/placebo) . The study comprises 147 children, 1-15 years of age, 83 boys and 64 girls, all with OME for more than three months . All the patients were candidates for tube insertion . In the group treated with erythromycin, 12 patients out of 69 had bilaterally air-filled middle ears after one month, as compared to 19 out of 72 in the group treated with the placebo . No difference was noted due to sex or age . The results support our indication and timing for ventilation tube insertion.

Klin Padiatr, 1990 Mar-Apr, 202(2), 120 - 3
Dientamoeba fragilis infection, a cause of gastrointestinal symptoms in childhood; Preiss U et al.; Clinical and laboratory findings of 123 paediatric patients with infections due to intestinal protozoa were analysed . Dientamoeba fragilis (D.f.) was found in 102 cases . The other patients had infections with Giardia lamblia or mixed infections with several other protozoa . Acute and recurrent diarrhoea were the most common findings (56 cases), whereas abdominal pain was more common in children with chronic symptoms . Peripheral eosinophilia was present in 32% of the children with dientamoebiasis . Metronidazole, oxytetracycline, doxycycline, and erythromycin were the most effective drugs in the treatment of D.f . infections . The therapy led coincidentally to the sanitation of stools and elimination of abdominal complaints . The investigations underline the pathogenic role of D.f . in those children with gastrointestinal symptoms . Mixed infections of D.f . and Enterobius vermicularis suggest a vector bound transmission of D.f.

Biochem Pharmacol, 1990 Mar 1, 39(5), 901 - 9
Purification of a sheep liver cytochrome P-450 from the P450IIIA gene subfamily . Its contribution to the N-dealkylation of veterinary drugs; Pineau T et al.; Oral administration of troleandomycin at a dose of 100 mg/kg/day for 6 days to three adult male Lacaune sheep produced a 1.6-fold increase in specific content of liver microsomal cytochrome P-450 . In sodium dodecyl sulfate-polyacrylamide gel electrophoresis, microsomal preparations from treated animals exhibited a strong band in the zone of electrophoretic mobility of cytochromes P-450 . This band corresponded to a cytochrome P-450 which cross-reacted with rabbit P450IIIA6 antibodies, as demonstrated by immunoblotting . The ovine isozyme was purified to electrophoretic homogeneity by means of successive DEAE cellulose, CM cellulose and hydroxylapatite chromatographic separations . This hemoprotein had an apparent molecular weight of 52 kD as determined by calibrated sodium dodecyl sulfate-polyacrylamide gel electrophoresis and was characterized in terms of spectral data, NH2-terminal amino acid sequence, immunologic and catalytic properties . This study revealed some interspecies differences with the orthologous rabbit isozyme . The contribution of this form to the N-demethylation of erythromycin and of three veterinary drugs: chlorpromazine, chlorpheniramine and bromhexine was demonstrated from inhibition by TAO, from immunoinhibition studies, using polyclonal antibodies raised in rabbit and from the existence of significant correlations between its microsomal level and these N-demethylase activities . In contrast, the results suggest that ovine P450IIIA could not be predominantly involved in the N-dealkylation of benzphetamine, ephedrine, ivermectine or spiramycin.

Laryngoscope, 1990 Mar, 100(3), 231 - 6
Head and neck sequelae of cardiac transplantation; Teixido M et al.; Cardiac transplantation has become the treatment of choice for end-stage cardiomyopathies . In 1987, nearly 2000 cardiac transplants were performed in the United States . Otolaryngologists will be asked with increasing frequency to evaluate and treat these patients . The otolaryngology service at Loyola University Medical Center has been involved in the follow-up and treatment of head and neck complications in 100 transplant patients . Sixty percent of these patients manifest head and neck sequelae . The results of this review are presented . The otolaryngologist should be aware of the special features of this patient population that require modification of the treatment approach, such as 1 . the need to avoid the drugs erythromycin, trimethoprim/sulfamethoxazole, and ketoconazole, 2 . the need to preserve the right internal jugular vein, and 3 . the high risk of silent myocardial infarction . A discussion of these treatment modifications is provided . All patients should be treated in close communication with the medical transplant treatment team.

Nihon Kyobu Shikkan Gakkai Zasshi, 1990 Mar, 28(3), 410 - 6
{Chronic bronchitis and related disorders}; Izumi T; Chronic bronchitis was a disease which attracted much attention in the U.K . in the 1950's . It was classified into three forms known as simple chronic bronchitis, recurrent or mucopurulent bronchitis, and chronic obstructive bronchitis and it was thought that the disease progressed from one form to the next in accordance with their order as listed here . Later, however, it was realized that the disease did not progress according to this order and that chronic bronchitis actually included three kinds of the disease . Furthermore, in the U.K., with the prohibition of the use of coal and the reduction of air pollution and with the decline of infectious disease in child age, recurrent or mucopurulent bronchitis underwent an extreme reduction . Chronic obstructive bronchitis is known to be caused by smoking and is now called chronic bronchitis and emphysema or COPD . Simple chronic bronchitis may in fact be only a simple physical response to smoking . Now in Japan the disease called chronic bronchitis is often recognized when written on receipts for health insurance, but patients of chronic bronchitis as were seen in the U.K . in the 1950's are extremely rare . Diffuse panbronchiolitis is seen in Japan but is a disease not found in the West . Diffuse bronchiectasis and its differentiation become the point of question for this disease . With the effectiveness of erythromycin, we can expect a decline in the number of patients and an improvement in prognosis.

An Esp Pediatr, 1990 Mar, 32(3), 225 - 7
{Rheumatic fever: clinical and therapeutic aspects}; Cadenas Gallego M et al.; From 1974 to 1987 we have diagnosed thirty three patients with rheumatic fever . The age of onset ranged from three to sixteen years with a mean age of nine years and six months . Carditis was the most frequent major criteria (27/33) followed by arthritis (14/33) and Sydenham's chorea (6/33) . All the patients with carditis had the mitral valve affected . The usual treatment in the acute phase was penicillin and aspirin . The prophylaxis recommended to the patients was penicillin G benzatine every 21 days if they had carditis and every 28 days if they didn't . Two patients allergic to penicillin are receiving erythromycin . We have observed that the incidence of rheumatic fever has remained unchanged that the age of onset increased and that the antiinflammatory drug of choice in most patients with carditis is aspirin.

Semin Respir Infect, 1990 Mar, 5(1), 30 - 7
Legionella infection in transplant patients; Ampel NM et al.; Since the discovery of Legionella pneumophila in the late 1970s, this organism and other Legionella sp have been an important cause of pneumonia in solid organ transplant recipients . Legionella sp are obligate aerobes that require a source of amino acids, iron, and L-cystine . Growth is enhanced in a 5% CO2 atmosphere at 37 degrees C in the presence of charcoal . Legionella sp reside in water supplies and hospital outbreaks associated with contaminated water have been described . Transplant recipients are particularly susceptible to Legionella infection . Legionella pneumonia tends to occur within several weeks after transplantation and frequently coincides with episodes of rejection . A prodrome of influenza-like symptoms is followed by a sometimes "explosive" pneumonia with patchy lobular or interstitial infiltrates on chest radiograph . High fever, abdominal pain, and mental status changes are sometimes seen . Diagnosis is made by examination of respiratory secretions by the direct fluorescent antibody technique or culture of the organism . Intravenous erythromycin is the treatment of choice . Rifampin is added if there is a lack of response . Both erythromycin and rifampin have important and opposite effects on cyclosporine metabolism, which may result, respectively, in increased cyclosporine toxicity or graft loss . Patients who must continue cyclosporine will, therefore, require frequent monitoring of cyclosporine levels.

Prim Care, 1990 Mar, 17(1), 85 - 93
Chlamydial infections; Graham JM et al.; Chlamydia causes many human infections and should be treated aggressively . Tetracycline or doxycycline are the drugs of choice, but erythromycin can be used if a drug allergy is present or if tetracyclines are contraindicated . In the pregnant woman, aggressive treatment can improve neonatal outcome . In the United States, each year 155,000 infants are exposed to Chlamydia trachomatis during the birth process, and more than 100,000 will be infected . Of these, 75,000 will get conjunctivitis, and 30,000 will get pneumonia . In pregnancy, erythromycin is the drug of choice, with treatment recommended after initial culture and at term if repeat cultures are positive . If erythromycin is not tolerated, or the patient has an allergy to it, ampicillin or clindamycin may be effective alternatives.

J Am Acad Dermatol, 1990 Mar, 22(3), 489 - 95
A clinical trial comparing the safety and efficacy of a topical erythromycin-zinc formulation with a topical clindamycin formulation; Schachner L et al.; One hundred three patients with acne vulgaris were randomly designated to receive either a topical formulation of erythromycin plus zinc or a topical solution of 1% clindamycin phosphate (Cleocin-T) . The patients treated themselves twice daily and were examined at 3, 6, 9, and 12 weeks after the start of therapy . By week 6 the overall severity grade was consistently lower and the percent reduction of severity, papules, pustules, and total comedones was higher in the erythromycin-zinc-treated group than in the clindamycin-treated group . In the 92 patients who completed this study (48 receiving erythromycin-zinc and 44 receiving clindamycin), no serious topical or systemic side effects were reported . Two patients, one from each treatment group, suffered mild irritation . One patient was withdrawn from the erythromycin-zinc-treated group . Results of patch tests were negative . The superiority of the erythromycin-zinc formulation may be due to the increased (4%) erythromycin concentration and/or the ability of 1.2% zinc acetate to enhance the product's activity.

Arch Biochem Biophys, 1990 Feb 15, 277(1), 166 - 80
Reconstitution of testosterone oxidation by purified rat cytochrome P450p (IIIA1); Halvorson M et al.; Cytochrome P450p (IIIA1) has been purified from rat liver microsomes by several investigators, but in all cases the purified protein, in contrast to other P450 enzymes, has not been catalytically active when reconstituted with NADPH-cytochrome P450 reductase and dilauroylphosphatidylcholine . We now report the successful reconstitution of testosterone oxidation by cytochrome P450p, which was purified from liver microsomes from troleandomycin-treated rats . The rate of testosterone oxidation was greatest when purified cytochrome P450p (50 pmol/ml) was reconstituted with a fivefold molar excess of NADPH-cytochrome P450 reductase, an equimolar amount of cytochrome b5, 200 micrograms/ml of a chloroform/methanol extract of microsomal lipid (which could not be substituted with dilauroylphosphatidylcholine), and the nonionic detergent, Emulgen 911 (50 micrograms/ml) . Testosterone oxidation by cytochrome P450p was optimal at 200 mM potassium phosphate, pH 7.25 . In addition to their final concentration, the order of addition of these components was found to influence the catalytic activity of cytochrome P450p . Under these experimental conditions, purified cytochrome P450p converted testosterone to four major and four minor metabolites at an overall rate of 18 nmol/nmol P450p/min (which is comparable to the rate of testosterone oxidation catalyzed by other purified forms of rat liver cytochrome P450) . The four major metabolites were 6 beta-hydroxytestosterone (51%), 2 beta-hydroxytestosterone (18%), 15 beta-hydroxytestosterone (11%) and 6-dehydrotestosterone (10%) . The four minor metabolites were 18-hydroxytestosterone (3%), 1 beta-hydroxytestosterone (3%), 16 beta-hydroxytestosterone (2%), and androstenedione (2%) . With the exception of 16 beta-hydroxytestosterone and androstenedione, the conversion of testosterone to each of these metabolites was inhibited greater than 85% when liver microsomes from various sources were incubated with rabbit polyclonal antibody against cytochrome P450p . This antibody, which recognized two electrophoretically distinct proteins in liver microsomes from troleandomycin-treated rats, did not inhibit testosterone oxidation by cytochromes P450a, P450b, P450h, or P450m . The catalytic turnover of microsomal cytochrome P450p was estimated from the increase in testosterone oxidation and the apparent increase in cytochrome P450 concentration following treatment of liver microsomes from troleandomycin- or erythromycin-induced rats with potassium ferricyanide (which dissociates the cytochrome P450p-inducer complex) . Based on this estimate, the catalytic turnover values for purified, reconstituted cytochrome P450p were 4.2 to 4.6 times greater than the rate catalyzed by microsomal cytochrome P450p.

J Am Acad Dermatol, 1990 Feb, 22(2 Pt 1), 253 - 60
Topical erythromycin and zinc therapy for acne; Schachner L et al.; A double-blind, 12-week study was undertaken to determine the safety and efficacy of a formulation of 4% erythromycin plus 1.2% zinc acetate compared with its vehicle . The study was continued for 40 weeks after the 12-week double-blind phase by switching vehicle-treated patients to active treatment and continuing to give patients treated with active drug the same treatment . Seventy-three female patients started the study; 39 completed 1 full year of study . In the first 12 weeks statistically significant differences were noted in the efficacy of the erythromycin-zinc compared with vehicle for acne severity grades (global assessment) and for papule, pustule, and comedo counts . After crossover, the vehicle-treated group receiving active therapy duplicated the improvement of the group initially treated with erythromycin-zinc . No clinical problems with superinfection or secondary infection occurred during 1 year of treatment in 39 patients.

Monatsschr Kinderheilkd, 1990 Feb, 138(2), 85 - 7
{Vitamin K deficiency with erythromycin . Observation of a boy treated with valproate}; Cordes I et al.; A nine year old boy had been treated with valproic acid during one and a half years because of a grand mal epilepsy . Under an additional medication with erythromycin succinate syrup this patient developed a deficiency of prothrombin-complex, which was reversible immediately after oral intake of vitamin K . In this case it is assumed that the simultaneous application of both valproic acid and erythromycin succinate seems to suppress the vitamin K producing intestinal tract bacteria, which has not been reported in the literature so far.

Pol Tyg Lek, 1990 Jan 22-29, 45(4-5), 82 - 4
{Occupational allergy in the production of drugs}; Rembadel P et al.; Quinazoline oxide--an intermediate in chlordiazepoxide synthesis--is the most potent contact allergen in the pharmaceutical industry . Penicillins proved to be potent allergens . Conditions of the technological process favor development of hypersensitivity to tetracyclines . No single case of allergy to erythromycin was noted . In case of employees hypersensitive to disulfiram and aminophylline cross reactions with compounds of similar structure were observed . The authors discuss also some problems concerning contact allergy in all persons occupationally dealing with various medicines.

Clin Ter, 1990 Jan 15, 132(1), 41 - 4
{Medical treatment of pelvic inflammatory disease . A clinical study on the therapeutic effectiveness of piperacillin + erythromycin and of piperacillin + clindamycin + gentamycin}; Sesti F et al.; The aim of the present clinical study was to evaluate the therapeutic effectiveness of two different antibiotic combinations (piperacillin + erythromycin and piperacillin + clindamycin + gentamycin) in the medical treatment of patients with pelvic inflammatory disease, respectively at the II and III stage . The findings confirm the therapeutic value and the low toxicity of both pharmacological regimens.

Cas Lek Cesk, 1990 Jan 12, 129(2), 56 - 7
{Acute ischemia of the extremities in the puerperal period}; Petr P et al.; The development of pharmacotherapy implies great advantages for patients, at the same time it is, however, also the source of more frequent side-effects of drugs, which may result also from mutual interactions of commonly used drugs . The authors describe a case of ergotism which developed as a result of drug interaction between the ergot uterotonic Cornutamine and the marcolid antibiotic Erythromycin . This interaction could have seriously damaged the health of the young woman . At the same time the authors remind of the clinical picture of ergotism and the possible way of its treatment . In the Czechoslovak literature no report on this interaction was published during the past three years.

Lancet, 1990 Jan 6, 335(8680), 11 - 5
Cyclosporin toxicity at therapeutic blood levels and cytochrome P-450 IIIA; Lucey MR et al.; A 40-year-old male liver allograft recipient had neurological dysfunction and renal failure while his cyclosporin blood levels were in the therapeutic range; these features recurred on rechallenge . The hypothesis that this toxic effect might have resulted from abnormal metabolism of cyclosporin by liver cytochrome P-450 IIIA was investigated with the {14C}erythromycin breath test, which is a measure of this enzyme's activity . P-450 IIIA activity was decreased compared with that in controls, including other liver transplant recipients . Pretreatment with rifampicin, an inducer of P-450 IIIA, increased enzyme activity . After treatment with rifampicin the patient could be rechallenged with cyclosporin at a dose almost twice that which had previously been toxic . The patient died during a second transplantation and the microsomal content of P-450 IIIA was found to be low in the first transplant.

Sex Transm Dis, 1990 Jan-Mar, 17(1), 48 - 50
Comparison of chlamydial culture with Chlamydiazyme assay during erythromycin PCE treatment of Chlamydia genital infections; Havlichek DH Jr et al.; We compared chlamydial culture with the chlamydial antigen detection enzyme immunoassay system (Chlamydiazyme, Abbott Diagnostic Products; Abbott Park, IL) during treatment of Chlamydia genital infections . Participants received 333 mg of erythromycin PCE (Abbott Laboratories; Abbott Park, IL) 3 times per day for 7 days . On days 0, 3, 7, and 14, chlamydial cultures were positive in 30/30 (100%), 5/29 (17.2%), 0/27, and 0/25 participants, respectively . Concurrent Chlamydiazyme assays were positive in 30/30 (100%), 11/30 (37%), 1/28 (4%), and 0/25 participants . Twenty-eight of 28 persons who received erythromycin PCE for at least 3 days had negative test results for both chlamydial culture and Chlamydiazyme at their last clinic visit . Chlamydiazyme assay tended to remain positive longer than chlamydial culture during treatment, but 7 days after therapy was completed, no Chlamydia trachomatis antigens were detectable by this assay . Erythromycin PCE was well tolerated and rapidly eliminated Chlamydia genital infections in 83% of persons showing negative cultures by the third day of therapy.

Mol Pharmacol, 1990 Jan, 37(1), 130 - 6
Effects of 4-alkyl analogues of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine on hepatic cytochrome P-450 heme, apoproteins, and catalytic activities following in vivo administration to rats; Riddick DS et al.; Various 4-alkyl analogues of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) cause mechanism-based inactivation of cytochrome P-450 (P-450) via heme destruction . We have examined the time course of effects of DDC analogues on the catalytic activities and apoproteins of the major beta-naphthoflavone-, dexamethasone-, and phenobarbital-inducible isozymes of rat liver P-450 following in vivo administration . In beta-naphthoflavone-treated rats, all DDC analogues examined caused loss of the P-450 chromophore and dramatic loss of 7-ethoxyresorufin O-deethylase activity, a catalytic marker for P-450c . The isopropyl, hexyl, and isobutyl analogues caused the most pronounced loss/alteration of P-450c apoprotein levels, as revealed by two monoclonal antibodies (MAbs), 1-31-2 and 1-7-1 . The apoprotein of P-450d was not altered . In dexamethasone-treated rats, all analogues except 4-hexyl-DDC caused loss of the P-450 chromophore and erythromycin N-demethylase activity, a catalytic marker for P-450p-related isozymes . Only 4-isopropyl-DDC caused significant loss/alteration of the apoprotein of P-450p-related forms, as revealed by MAb 2-13-1 . In phenobarbital-treated rats, all analogues reduced the level of the P-450 chromophore, whereas only 4-hexyl-DDC and 4-isopropyl-DDC lowered 7-pentoxyresorufin O-dealkylase activity, a catalytic marker for P-450b . MAbs 2-66-3 and 2-8-1 revealed no change in the level of phenobarbital-inducible apoproteins recognized by these probes . In agreement with our previous in vitro studies {Mol . Pharmacol . 35;626-634 (1989)}, P-450 c and p are targets for mechanism-based inactivation by DDC analogues . However, unlike the situation in vitro, loss of enzyme activity in vivo is, at least in some instances, accompanied by loss/alteration of the corresponding P-450 apoprotein.

Am Rev Respir Dis, 1990 Jan, 141(1), 72 - 8
Erythromycin inhibits respiratory glycoconjugate secretion from human airways in vitro; Goswami SK et al.; Erythromycin and other antibiotics have been used empirically in the treatment of patients with chronic obstructive pulmonary disease (COPD) . We studied whether this empirical role of antibiotics might not be related to a possible direct effect on respiratory glycoconjugate (RGC) secretion . The effect of erythromycin on RGC secretion and hypersecretion was studied in an in vitro preparation of human airways that were secreting {3H}glucosamine respiratory glycoconjugate (RGC), and on a human endometrial adenocarcinoma cell line secreting a glycoconjugate (tumor glycoconjugate = TGC) chemically similar to the RGC secreted by the airways . Erythromycin at 10(-5) M reduced RGC secretion by 35 +/- 4% (n = 9, p less than 0.001) in both human airways and the adenocarcinoma cells, and was increasingly active in the pharmacologic range of 10(-7) to 10(-4) M . The inhibitory effect of erythromycin was maximal within 16 h and was still evident 34 h after incubation . Erythromycin was noted to reduce both spontaneous (baseline) and stimulated RGC secretion (by histamine and methacholine) from airways in culture . The blocking effect appeared to be more selective for histamine than methacholine . These effects were not associated with any toxicity to the tissues and were not associated with the inhibition of protein synthesis . Dexamethasone also inhibited RGC release in both assay systems and exhibited dose-related effects in the physiologic ranges (10(-9) to 10(-5) M) . When administered together, erythromycin and dexamethasone had an additive inhibitory effect on RGC secretion (68.0 +/- 3.0%, n = 7, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Rev Esp Anestesiol Reanim, 1990 Jan-Feb, 37(1), 28 - 31
{Severe heart arrhythmia secondary to magnesium depletion . Torsade de pointes}; Papaceit J et al.; We report a case of torsade de pointe ventricular tachycardia in a patient with chronic magnesium depletion . The etiological aspects implicated this unusual cardiac arrhythmia are: the congenital long QT syndrome; bradycardia, either sinusal or due to atrioventricular block; ionic depletions: hypokalemia, hypocalcemia and hypomagnesemia; treatment with antiarrhythmic class AI drugs (quinidine-like agents), tricyclic antidepressants, phenothiazines and erythromycin; organophosphate poisoning . After ruling out other factors, we concluded that it was caused by hypomagnesemia on the basis of laboratory findings and the good response to replacement therapy . We then discuss the several types of therapy proposed for this arrhythmia; finally, we emphasize the major role of magnesium in myocardial repolarization.

Pharmacol Toxicol, 1990 Jan, 66(1), 49 - 52
Cyclosporin metabolism in human liver microsomes and its inhibition by other drugs; Henricsson S et al.; The metabolism of cyclosporin was studied in human liver microsomes . There was no metabolism in the presence of cytochrome C or carbon monoxide or in the absence of cofactors, suggesting metabolism by cytochrome P-450 enzymes . The metabolism was inhibited by ketoconazole and erythromycin, by the steroids methylprednisolone and oestradiol, and by the calcium antagonists diltiazem, nifedipine, prenylamine and verapamil . These in vitro findings correlate well with previously published clinical reports suggesting that these drugs may inhibit the metabolism of cyclosporin in vivo . Our observations suggest that metabolic interactions between cyclosporin and other drugs in vivo may be predicted in vitro under proper experimental conditions.

J Clin Pharmacol, 1990 Jan, 30(1), 39 - 44
Effect of concurrent sucralfate administration on the absorption of erythromycin; Miller LG et al.; To determine the influence of sucralfate on the absorption of erythromycin, prior to evaluating its efficacy in decreasing erythromycin-associated gastrointestinal (GI) intolerance, we assessed pharmacokinetic parameters in six healthy adult volunteers . Erythromycin ethylsuccinate administered alone or with sucralfate as a single dose was compared . Sucralfate did not significantly alter the elimination rate constant, half-life, or area under the curve for erythromycin ethylsuccinate . It is therefore unlikely that efficacy of erythromycin ethylsuccinate will be altered when sucralfate is coadministered.

Arch Intern Med, 1990 Jan, 150(1), 215 - 6
Fulminant hepatic failure associated with intravenous erythromycin lactobionate; Gholson CF et al.; Fatal fulminant hepatic failure accompanied by brisk hemolysis developed in an elderly man after intravenous administration of erythromycin lactobionate for a lower respiratory infection . To our knowledge, this is the first case of fatal hepatotoxicity associated with intravenous erythromycin therapy . Erythromycin should be added to the list of drugs that can cause fulminant hepatic failure.

Mikrobiyol Bul, 1990 Jan, 24(1), 41 - 7
{Prevention of wound infection in elective colon surgery by the use of systemic ceftriaxone and ornidazole}; Alhan E et al.; In this study prophylactic effects of ceftriaxone and ornidazole on the patients undergoing elective colon surgery was studied in the surgical clinics, Medical Faculty of Karadeniz Technical University . Colon cleaning with Nichol's method was performed in all cases . But kanamycin and metronidazole were given instead of erythromycin and metronidazole . One hour before the operation ceftriaxone 1 gr . and ornidazole 500 mg . (IV, IM) were administered . Those antibiotics were followed by ceftriaxone 2 gr . daily and ornidazole 1 gr . daily (IV, IM) three days after operation . The wound infection were observed in the postoperative period (5%) . The average hospitalization time of the cases were 12 days . This period was 18 days and 21 days in the cases having infection . Side effects related the drugs were not observed and there were no significant laboratory changes.

Food Addit Contam, 1990, 7 Suppl 1, S127 - 30
Cytoprotective effects of Gypsophila saponins towards isolated rat hepatocytes; Braut-Boucher F et al.; Saponins are glycosides widely distributed in the plant kingdom and are found in many foods . The hepatoprotective potential of glucuronogypsogenin (GG) and gypsoside (GY) towards isolated rat hepatocytes treated by three toxic models used at sub-lethal doses: galactosamine (5 x 10(-3) M), CCl4 (5 x 10(-4) M) and erythromycin (5 x 10(-4) M) was investigated . Two schedules were carried out corresponding to curative or preventive treatment . No protection was observed on hepatocytes treated with GY before or after addition of the toxicants . In contrast, a protective action was detected when hepatocytes were pretreated with GG (5 x 10(-5) M) as probe, by the normalisation of LDH leakage and ATP content . It depends on the toxicant: the cytoprotective spectrum is 5 x 10(-5) to 5 x 10(-7) M with galactosamine; 5 x 10(-5) to 5 x 10(-6) M with CCl4; and around 5 x 10(-5) M with erythromycin . Taking into account the importance of LDH as an indicator of membrane damages, GG was assumed to interact with membrane hepatocyte.

Eur J Clin Pharmacol, 1990, 39(2), 161 - 4
Effect of age on single- and multiple-dose pharmacokinetics of erythromycin; Miglioli PA et al.; The effect of age on the pharmacokinetics of erythromycin was investigated by comparing its kinetic behaviour in eight young healthy adults and eight healthy elderly subjects after single and repeated oral doses of erythromycin stearate 1 g b.d . for 7 doses . The peak serum concentration and area under the serum concentration-time curve (AUC) were significantly greater in the elderly subjects than in the young controls after single and multiple doses . Accordingly, the apparent oral clearance was lower in the elderly subjects (0.31 vs 0.64 and 0.22 vs 0.69 l.h-1.kg-1 after the first and seventh administration, respectively) . The mean elimination half-life was significantly longer in the elderly group only after multiple dosing (4.8 vs 2.3 h) . No age-related difference was observed in the time to peak serum concentration and apparent volume of distribution . The multiple-dose regimen resulted in an almost two-fold accumulation of erythromycin in the older individuals and no accumulation in the young adults . Mean drug accumulation in elderly subjects at steady state was 43% greater than was predicted from the AUC after the first dose, suggesting a time-dependent reduction in both systemic and presystemic clearance . The results indicate that the metabolic elimination processes for erythromycin are impaired in normal elderly subjects and suggest that caution is required on administering a high dose of it to aged people.

Padiatr Grenzgeb, 1990, 29(4), 291 - 4
{Chlamydia-induced pneumonia in children}; Drak D et al.; Three cases of pneumonia caused by Chlamydia were observed . The disease ran a protracted course and was refractory to treatment . Erythromycin was given initially intravenously and then orally, with improvement of the general condition of children and regression of inflammatory changes in the lungs . Such cases are worth of reporting in view of only isolated reports on respiratory infections caused by these organisms.

J Antimicrob Chemother, 1990 Jan, 25 Suppl A, 91 - 9
Efficacy of azithromycin for therapy of active syphilis in the rabbit model; Lukehart SA et al.; Azithromycin was shown to be as effective as standard benzathine penicillin and erythromycin in the therapy of active syphilis in the rabbit model . Following production of primary chancres by intradermal inoculation of 10(6) Treponema pallidum, groups of six rabbits were treated with benzathine penicillin (200,000 units im weekly for two weeks), erythromycin base (30 mg/kg/day orally four times daily for 15 days) or azithromycin (30 mg/kg/day given orally once or twice daily for 15 days); one group was untreated . Daily darkfield (DF) microscopic examinations of chancre aspirates were conducted to identify motile organisms . Although all treated animals became DF negative prior to completion of therapy, the median time to DF negativity was longer in animals given azithromycin once daily, compared with animals receiving benzathine penicillin (P less than 0.01); no difference was seen in comparison with animals receiving erythromycin . Untreated animals remained DF positive for greater than 15 days . The mean maximum lesion diameters for all treated animals were similar and were significantly smaller than in untreated rabbits; fewer lesions ulcerated in treated than in untreated animals . Subsequent dose-ranging studies indicated that administration of lower doses of azithromycin (15 mg/kg/day given orally either once or twice daily, or 7.5 mg/kg/day given once daily) was as effective as benzathine penicillin for therapy of active syphilis in this model, though the median time to darkfield negativity was significantly longer in the azithromycin-treated animals (P less than 0.01) . Persistent infection was demonstrable in lymph nodes of untreated animals, but no evidence of virulent T . pallidum was found three months following transfer of tissue from any animal treated with penicillin, erythromycin, or azithromycin.

J Antimicrob Chemother, 1990 Jan, 25 Suppl A, 123 - 6
Comparison of azithromycin and erythromycin in the treatment of atypical pneumonias; Schonwald S et al.; An open, randomized, multicentre study compared the efficacy and safety of the prototype, azalide, azithromycin, and erythromycin in the treatment of atypical pneumonias . Azithromycin was administered for five days at a dosage of 250 mg bd on day 1 and 250 mg once daily on days 2 to 5 . Erythromycin was given for ten days at 500 mg qid . Causative pathogens were identified by serological methods . Of 57 patients treated with azithromycin, Mycoplasma pneumoniae and Chlamydia psittaci were identified in 31 and eight patients, respectively . Of 44 patients treated with erythromycin, M . pneumoniae and C . psittaci were identified in 24 and eight patients, respectively . There were no therapeutic failures in either treatment group . Side effects were observed in one of 57 patients on azithromycin and in six of 44 patients on erythromycin . Azithromycin appears to be as effective as erythromycin in the treatment of atypical pneumonias and better tolerated.

J Antimicrob Chemother, 1990 Jan, 25 Suppl A, 101 - 8
Efficacy of azithromycin in the treatment of guinea pigs infected with Legionella pneumophila by aerosol; Fitzgeorge RB et al.; Azithromycin and erythromycin were compared for efficacy in guinea pigs infected with an aerosol containing Legionella pneumophila . When administered intraperitoneally, azithromycin was very effective in the treatment of experimental Legionnaires' disease . Even at the low dose of 3.6 mg/kg/day it gave 100% survival and eliminated lung infectivity two days following infection . In contrast, erythromycin at a much higher dose (96 mg/kg/day) gave only 83.3% survival and failed to eliminate organisms from the lung six days after infection . The histological findings confirmed the superiority of azithromycin . A single dose of azithromycin given intraperitoneally at 3.6 or 14.4 mg/kg gave survival rates of 83.3 and 100%, respectively . Azithromycin was also found to be superior to erythromycin in eliminating lung infectivity and reducing mortality, when administered orally . However, oral administration of azithromycin was not as effective as intraperitoneal when assessed by lung histopathology, although it was still superior to oral erythromycin treatment.

Przegl Dermatol, 1990 Jan-Feb, 77(1), 56 - 60
{Akne-Mycyna in the local treatment of acne}; Rubisz-Brzezinska J et al.; Akne-Mycyna, a new preparation for external treatment of acne containing 1% erythromycin, was used in 30 cases of acne: 12 cases of papulo-pustolous acne, 13 with pustulous acne, 5 with acne conglobata . The age of the patients ranged from 16 to 27 years, the mean duration of acne was 3.5 years . Selected lesions were smeared with Akne-Mycyna twice daily, mostly on one side of the face; symmetrical lesions were treated by conventional external methods . In the light of the study it is concluded that Akne-Mycyna is a very effective preparation for external treatment of papulo-pustulous acne and in milder cases of pustulous acne, with the duration of treatment at least 3 weeks . In deep forms of acne, particularly acne conglobata, Akne-Mycyna may be a valuable supplementation of systemic treatment.

Rev Elev Med Vet Pays Trop, 1990, 43(4), 453 - 5
{In vitro antibiosensitivity of different strains of Mycoplasma capricolum}; Benkirane A et al.; The in vitro sensitivity of 20 wild strains of M . capricolum and that of the reference strain (California kid) against 14 antibiotics was investigated by means of a micromethod . The technique is based on the determination of the inhibitory minimum concentration (IMC) in a liquid medium as revealed by the inhibition of glucose metabolism . The following results were obtained: all strains were sensitive to five antibiotics (tylosin, oxytetracyclin, gentamycin, neomycin, nalidixic acid) with an IMC varying from 0.06 to 8 meq/ml . The variation in the IMC values from 8 to 32 meq/ml for spiramycin and erythromycin indicated that some of these strains were sensitive and other resistant to these two drugs . All strains were resistant to seven antibiotics (streptomycin, bacitracin, polymyxin, chloramphenicol, lincomycine, rifampicine and novobiocine), sometimes at a concentration exceeding 128 meg/ml.

Boll Ist Sieroter Milan, 1990, 69(1), 319 - 31
{Validity limits of data on secretory IgA}; Rosaschino F et al.; Secretory IgA (sIgA) in saliva, and sometimes in expectoration, have been titrated in various groups of persons, both in pediatric age and in adults, by means of radial immunodiffusion technic . The aim was to find differences among sIgA levels in the course of respiratory tract infections, both acute and chronic, in consequence of treatment with Erythromycin (in children and in adults) in consequence of surgical intervention (in adults) . Adjunctive aim was to establish if it was possible to recognize hereditary of the character that remark the predisposition to produce high sIgA quantities . The very high variability of the data collected in the various occasions and situations allowed serious doubts about the possibility of use of the parameter sIgA in saliva for the evaluations that were assumed as aim of the research . The said high variability was confirmed in a single surely healthy boy, in which sIgA were performed on saliva specimens collected for ten consecutive days, morning and evening, always at the same time (8 a.m . and p.m.) . In the attempt to clarify the reason of such a variability, the intervention of psychical solicitation and emotional conditions were ipotized to modify production, mobilization and secretion of IgA generally considered and sIgA particularly.

Ann N Y Acad Sci, 1990, 590, 168 - 86
Interferon-alpha/beta and Rickettsia prowazekii: induction and sensitivity; Turco J et al.; Rickettsia prowazekii Madrid E established persistent infections in cultures of growing L-929 cells . Although some L-929 cells died, the cultures survived, remained infected with rickettsiae, and continued to grow . R . prowazekii Madrid E also induced interferon in L-929 cell cultures, and this interferon modulated rickettsial growth . Production of interferon (anti-viral activity) by cultures of R . prowazekii-infected L-929 cells was directly related to the initial rickettsial infection and was blocked by erythromycin . The media collected from R . prowazekii-infected L-929 cells suppressed not only the replication of vesicular stomatitis virus but also the growth of R . prowazekii in fresh L-929 cells . Both anti-viral and anti-rickettsial activities in the media were neutralized by antibodies against murine interferons-alpha and -beta, but not by antibodies against murine interferon-gamma . In addition, a commercial preparation of virus-induced interferons-alpha and -beta also suppressed rickettsial growth in L-929 cells . The combination of treating L-929 cells with this virus-induced interferon and infecting them with R . prowazekii killed some of the L-929 cells.

Ren Fail, 1990, 12(4), 241 - 8
Primary renovascular effects of erythromycin in the rat: relationship to cyclosporine nephrotoxicity; McCormack AJ et al.; Erythromycin is known to exacerbate cyclosporine nephrotoxicity . This has been attributed to the potential of erythromycin to reduce the hepatic microsomal metabolism and clearance of cyclosporine . Erythromycin may also be nephrotoxic . We tested the hypothesis that erythromycin may have direct effects on the renal vasculature which are additive or synergistic with the effects of cyclosporine . Sprague-Dawley rats were administered graded doses of either erythromycin, 2.5, 5, 7.5, and 10 mg/kg BW/min i.v . over consecutive 10-min intervals; cyclosporine, 1, 2, 3, and 4 mg/kg BW/min i.v . over consecutive 10-min intervals; or both drugs simultaneously . In separate experiments, identical doses of erythromycin or cyclosporine were infused intravenously following acute unilateral renal denervation . Infusion of erythromycin led to an initial decline in arterial blood pressure whereas infusion of cyclosporine resulted in a dose-related increase in arterial blood pressure . Despite these different systemic effects, each drug alone produced a striking decrease in renal blood flow . This effect was more pronounced when the drugs were infused concomitantly . The reduction in renal blood flow occurred in an additive manner as a direct consequence of increased renal vascular resistance . Prior renal denervation did not modify the response to either erythromycin or cyclosporine . These results demonstrate that cyclosporine-induced vasoconstriction is exacerbated by erythromycin and suggest that the decline in renal function observed in patients coadministered these drugs may be due in part to additive renovascular toxicity.

Eur J Clin Pharmacol, 1990, 39(6), 555 - 8
Effect of erythromycin on the oro-caecal transit time in man; Lehtola J et al.; Erythromycins often cause gastrointestinal side-effects due to an increase in motility or to change in the intestinal bacterial flora . In order to evaluate the effect of erythromycin on gastrointestinal motility . 11 healthy volunteers were given placebo, erythromycin stearate (ES) 1000 mg or a therapeutically equivalent single dose of erythromycin acistrate (EA.2'-acetyl erythromycin stearate) 800 mg in a double-blind trial . The oro-caecal transit time was measured using the hydrogen breath test with lactulose as the substrate . The transit time was estimated from the H2-peak (ppm) in end-expiratory breath by two methods, t1 representing the "front" and t2 the "bulk" of lactulose reaching the colon . t1 was 51 min in the placebo group, 38 min in the EA and 31 min in the ES group (p less than 0.05, ES vs placebo) . t2 was 74 min, 64 min, and 46 min, respectively (p less than 0.05, ES vs placebo) . The difference between EA and ES was also significant . Six subjects in the ES group but none in the EA group recorded adverse gastrointestinal effects attributable to medication . It was concluded that erythromycin shortens the oro-caecal transit time in man and that EA effects the transit time slightly less than ES.

Ther Hung, 1990, 38(4), 152 - 5
Use of a new erythromycin product--eryc--in the treatment of the lower respiratory tract infections; Adam A et al.; Eryc therapy was used in 27 patients admitted with acute exacerbation of chronic obstructive bronchitis, and in 4 patients with pneumonia . Depending on the severity of the condition the dose of the drug was 4 x 500 mg or, in a lower number of cases, 4 x 250 mg . The effectivity of therapy was evaluated on the basis of the changes in the quality of sputum, elimination of facultative pathogens identified from sputum at admittance, clinical symptoms, respiratory function values, blood gas values, and, in case of pneumonia, improvement of chest X-ray finding . Eryc therapy proved to be effective in 78.6% of the cases . Side-effects were observed in 25.8% of the cases but the therapy had to be discontinued because of the severity of unwanted effects only in 3 patients (9.7%) . The change of the method of drug administration-intake during meals-did not decrease the frequency of side-effects when compared to Hungarian data . On the basis of our results Eryc therapy was found to be useful for the treatment of the lower respiratory tract, community-acquired infections.

Pharmacology, 1990, 41(4), 177 - 83
Enhanced interleukin production after long-term administration of erythromycin stearate; Kita E et al.; The effects of erythromycin stearate (10 mg/kg/day) were studied on productions of interleukin (IL)-1 and -2 in mice after a long-term treatment . A 28-day treatment resulted in higher levels of IL-1 production by macrophages and of IL-2 production by splenocytes, while a 7-day treatment did not increase them . T-cell growth factor activity of IL-2 preparation prepared on day 28 of treatment as determined by HT-2 cell proliferation was reduced by about 40% in the presence of anti-murine IL-4 monoclonal antibodies, while control IL-2 activity was not reduced . Furthermore, a 28-day treatment with erythromycin stearate increased concanavalin A-induced blastogenesis of splenocytes significantly . These results suggest that long-term treatment with erythromycin stearate can stimulate host defense by increasing interleukin production.

Comp Biochem Physiol C, 1990, 96(1), 111 - 4
Comparison of hepatic drug metabolizing enzymes in three-month-old lambs and kids; Kaddouri M et al.; 1 . The comparative activity of hepatic cytochrome P-450 monooxygenase system, glucuronyl-transferase, glutathione S-transferase and N-acetyltransferase was studied in three-month-old male and female Lacaune lambs and male Saanen kids . 2 . The study of mixed-function oxidase components showed that total cytochrome P-450 ranged from 0.54 in kids to 0.85-0.88 nmol/mg-1 in lambs . Male lambs had higher levels than kids (122-165%) for aminopyrine, benzphetamine, ethylmorphine and erythromycin demethylases or benzo(a)pyrene hydroxylase whereas NADPH-cytochrome c reductase was 1.19-fold lower in lambs . 3 . Sex-related changes were observed in lambs in case of microsomal benzo(a)pyrene hydroxylase activity which appeared 1.31-fold more potent in male liver . Cytosolic N-acetyltransferase accepting sulfamethazine as substrate was about 8-fold higher in female than in male lambs . 4 . The analysis of samples from various liver lobes, indicated the heterogenous distribution of microsomal proteins which is related to higher concentrations of both cytochrome b5, NADPH-cytochrome c reductase and p-nitrophenol glucuronyltransferase in left lobes.

Acta Derm Venereol, 1990, 70(3), 269 - 71
Roxithromycin and erythromycin in chlamydia-negative non-gonococcal urethritis; Worm AM; The clinical efficacy and safety of roxithromycin 300 mg once a day was compared with that of erythromycin 500 mg twice a day in 87 men with chlamydia-negative non-gonococcal urethritis . In the roxithromycin group the clinical efficacy rate was 88% on day 8 and between 78% and 84% on day 21 . In the erythromycin group the clinical efficacy rate was 98% on day 8 and 86% on day 21, a non-significant difference . Side effects were mainly gastrointestinal, occurring in about 15% of patients receiving each treatment.

Ann Cardiol Angeiol (Paris), 1989 Dec 30, 38(10), 657 - 9
{Jet intravenous injection of erythromycin lactobionate . A possible cause of the occurrence of crisis in torsade de pointe}; Camilleri JF et al.; The authors report one case of torsade de pointe which occurred immediately after fast intravenous injection of a 1-gram dose of erythromycin lactobionate in a female patient who had undergone surgical replacement of the mitral and triscuspid valves 24 hours before . The responsibility of erythromycin was strongly suggested by the clinical data (syncope), electrocardiographic findings (electrocardiogram typical of torsade de pointe, slow rhythm and lengthened QT interval in the basal ECG) and the chronology of the sequence of intravenous injection of the antibiotic and the rhythm disorder . A literature search revealed six similar cases . Its seems that the arrythmogenic property of this drug is related to abnormally elevated serum levels following rapid administration.

Schweiz Med Wochenschr, 1989 Dec 16, 119(50), 1834 - 6
{Drug interactions of midazolam}; Gascon MP et al.; Midazolam is a short-acting benzodiazepine with a short half life (1.5-2.5 h) due to intense biotransformation by liver monooxygenases . Anecdotal clinical reports have mentioned a wide interpatient variability in its duration of action . We investigated by in vitro screening factors that could interfere with the rate of midazolam biotransformation (drug-drug interactions) . Metabolite production (1'-and 4-OH-midazolam) was monitored in human liver microsomes . Midazolam hydroxylations are inhibited by several drugs (i.e . erythromycin, phenothiazine-type neuroleptics, cyclosporine) . The clinical relevance of these drug interactions is illustrated by the example of a patient treated with amiodarone, erythromycin and midazolam during anesthesia . Midazolam-induced sleep lasted about 6 days due to inhibition of its biotransformation by concomitant drug treatment.

Pediatr Dermatol, 1989 Dec, 6(4), 267 - 74
Pemphigoid in children; Oranje AP et al.; Pemphigoid is an autoimmune blistering disease that is rare in childhood . A review of the English, German, and French literature published prior to 1989 revealed 31 cases of juvenile bullous pemphigoid and 12 of other forms (10 cases of juvenile cicatricial and 2 of juvenile localized bullous pemphigoid) . Childhood pemphigoid, although less frequent, seems no different than its adult counterpart . While oral lesions are more common in the juvenile bullous form, there is no association with malignancy, which is a controversial and presumably incorrectly assumed association in the adult disease . The prognosis for children is good in most cases, and the disease is self-limiting . The mainstay of therapy has been oral corticosteroids, but dapsone also often produces a good response . A relatively new approach is to give a combination of erythromycin and niacinamide with dapsone for a steroid-sparing effect . In some patients the response to erythromycin plus niacinamide alone has been satisfactory; however, controlled therapeutic trials are lacking . It has been stated that high doses of steroids and immunosuppressive drugs are indicated for the cicatricial, as opposed to juvenile, bullous pemphigoid . From this review of the few cases of childhood cicatricial disease, it seems that the therapeutic approach might be the same for both forms.

J Pharm Sci, 1989 Dec, 78(12), 1015 - 9
Tetracycline and erythromycin distribution in pathological lungs of humans and rat; Fournet MP et al.; Tetracycline and erythromycin concentrate highly in pulmonary tissues in humans as well as in the rat . Their binding to the lung, whatever the species and the pathological state, is weak . Their intrapulmonary concentrations could be explained by a passive diffusion which depends on the pH variation between the intra- and extratissue compartments, the percentage of un-ionized form present, and their liposolubility . The importance of retention of tetracycline and erythromycin by plasma proteins is demonstrated by the decrease of their pulmonary index of penetration (IP, the intra- and extratissue concentrations ratio) . The IP values are, respectively, 1.09 and 1.23 for tetracycline and erythromycin . These concentrations are in excess of their minimal inhibitory concentrations for bacteria responsible for pneumopathies . The lung homogenate binding of these antibiotics is weak (5% for erythromycin and 33% for tetracycline), corresponding to a nonsaturable binding to three main subcellular fractions (nucleus, mitochondria, and cytosol) . Tetracycline has the same penetration in healthy or cancerous human lungs, whereas erythromycin presents a decreased IP in cancerous tissue . However, the binding of these antibiotics to healthy or cancerous lung homogenates is similar . So, the structure of cancerous cells is solely responsible for this modification of erythromycin penetration . The intrapulmonary concentration of tetracycline is increased in rat lungs infected by Legionella pneumophila . This modification is due to a great bacteria retention . In contrast, erythromycin possesses the same IP in healthy and infected rat lungs.

J Gen Microbiol, 1989 Dec, 135 ( Pt 12), 3281 - 8
Inducible ribosomal RNA methylation in Streptomyces lividans, conferring resistance to lincomycin; Jenkins G et al.; Streptomyces lividans TK21 possesses inducible ribosomal RNA methylase activity that confers high-level resistance to lincomycin and lower levels of resistance to certain macrolides . The methylase gene (designated lrm) is inducible by erythromycin and other macrolides and also by celesticetin (a lincosamide) but not by lincomycin . The lrm enzyme monomethylates the N6-amino group of adenosine at position 2058 within 23S-like ribosomal RNA.

Minerva Chir, 1989 Nov 30, 44(22), 2337 - 40
{Short-term prophylaxis with erythromycin lactobionate in patients undergoing lung surgery}; Mineo TC et al.; The efficacy of short term prophylaxis with erythromycin lactobionate in the peri-operative treatment in patients undergoing pulmonary surgery is examined.

Arch Dermatol, 1989 Nov, 125(11), 1543 - 7
Bacillary (epithelioid) angiomatosis and concurrent Kaposi's sarcoma in acquired immunodeficiency syndrome; Berger TG et al.; Two patients with acquired immunodeficiency syndrome developed simultaneous Kaposi's sarcoma and bacillary (epithelioid) angiomatosis . The distinguishing clinical and histologic features of these two vascular proliferations associated with human immunodeficiency virus disease are described . The lesions of bacillary (epithelioid) angiomatosis contained bacteria, while the lesions of Kaposi's sarcoma did not . With erythromycin therapy, the lesions of bacillary (epithelioid) angiomatosis cleared, while those of Kaposi's persisted . Bacillary (epithelioid) angiomatosis, a treatable but potentially fatal opportunistic infection of human immunodeficiency virus disease, should be considered in the differential diagnosis of vascular lesions in immunosuppressed patients.

Obstet Gynecol, 1989 Nov, 74(5), 687 - 93
Congenital syphilis: the University of Miami/Jackson Memorial Medical Center experience, 1986-1988; Ricci JM et al.; Between January 1, 1986 and July 1, 1988, 56 cases of congenital syphilis were identified at the University of Miami/Jackson Memorial Medical Center . The overall rate was 18.4 cases per 10,000 births, with a threefold increase found from 1986 to 1988 . A case-control study using matched pairs was done to identify differences in maternal demographics and pregnancy outcome . Congenital syphilis case mothers were predominantly black American women who lacked prenatal care (67%) and who were substance abusers (71%) significantly more often than their matched controls (P less than .005) . Three cases of seroconversion in pregnancy were identified . Failure to screen or inappropriate treatment occurred in four patients . Seven women were treated during pregnancy: Five received benzathine penicillin G for 3 consecutive weeks and two received erythromycin . All treated patients presented for initial care in the late second or third trimester . Thirty-seven infants (66%) were live-born and 19 (34%) were stillborn . Preterm labor and premature rupture of the membranes were significantly more common in infected pregnancies than in controls (P less than .005) . Live-born case infants had significantly lower birth weights than controls (P less than .005), with 21% of case infants growth-retarded . Seven neonatal deaths and one infant death occurred . The resultant perinatal mortality rate from congenital syphilis in this series was 464 pe 1000.

J Pharmacol Exp Ther, 1989 Nov, 251(2), 707 - 12
An erythromycin derivative, EM-523, induces motilin-like gastrointestinal motility in dogs; Inatomi N et al.; The effect of an erythromycin derivative, EM-523, on gastrointestinal motility was investigated in conscious dogs and compared with that of motilin cisapride, trimebutine and metoclopramide . In the fasting state, EM-523 given i.v . or i.d . at 3 micrograms/kg or more induced contractions in the stomach that migrated along the small intestine . The pattern of the contractions was very similar to that induced by motilin . In the digestive state, EM-523 increased the amplitude of gastric contractions . Cisapride and metoclopramide increased gastrointestinal motility both in the fasting and digestive states; however, their contractile pattern was different from that of EM-523 . Trimebutine did not induce gastric motility in the fasting state but rather decreased gastric motility in the digestive state . The contractions induced by EM-523 and motilin were inhibited by atropine but were not affected by naloxone, suggesting that the cholinergic pathway is important in the exertion of their action . These results indicate that EM-523 mimics motilin in stimulating gastrointestinal motility and that this agent may be useful treat gastrointestinal disorders such as gastric stasis, gastroesophageal reflux, and postoperative ileus, and so forth.

Arch Biochem Biophys, 1989 Nov 1, 274(2), 355 - 65
Characterization of a cDNA encoding a new member of the glucocorticoid-responsive cytochromes P450 in human liver; Schuetz JD et al.; Adult human liver contains a form of cytochrome P450, termed HLp, that resembles the glucocorticoid-inducible cytochrome P450p in rat liver in its structure, function, and regulation and catalyzes the oxidation of such clinically important substrates as cyclosporin, nifedipine, erythromycin, and midazolam . Recent evidence, however, suggests that HLp may represent two or more closely related forms of cytochromes P450, one of which is termed P450nf . To search for additional members of the Class III human subfamily of HLp related genes, we screened a human liver cDNA library cloned in phage vector lambda gt11 with oligonucleotides and with a cDNA fragment related to HLp . We isolated a full-length cDNA (1709 nucleotides) encoding a new form of human cytochrome P450 termed HLp2 . Analysis of HLp2 cDNA predicted a protein of 502 amino acids, weighing 57,294 Da 83% similar to HLp . HLp2 appears to represent a distinct gene as judged by partial sequence analysis of a cloned human gene and by hybridizations of Southern blots, under conditions of varying stringency, with a 3'-portion of HLp cDNA and with an oligonucleotide specific for HLp2 . Northern blot analysis revealed that HLp/P450nf was present in all samples of liver mRNA from adult patients not treated with inducers of HLp, whereas HLp2 mRNA was undetectable in more than two-thirds . Human fetal liver RNA contained mRNA species 2.1 and 1.9 kb which hybridized with an HLp2 oligonucleotide . We conclude that HLp2 represents a third member of the Class III glucocorticoid-responsive gene family that is expressed in both fetal and adult human liver and may account for polymorphism in metabolism of clinically important drugs.

Clin Ther, 1989 Nov-Dec, 11(6), 812 - 9
Comparison of oral erythromycin ethylsuccinate and clavulanate-potentiated amoxicillin in the treatment of acute respiratory tract infections; Shanks N et al.; Seven hundred fifty patients with acute upper or lower respiratory tract infections were randomly assigned to receive 2 gm of erythromycin ethylsuccinate daily or 1.125 gm of clavulanate-potentiated amoxicillin daily in a single-blind, multicenter study . The efficacy of each formulation was similar, with close to 90% of patients in each treatment group being reported as either cured or improved . Gastrointestinal symptoms were the most commonly reported side effects, their overall incidence being similar in both treatment groups . However, diarrhea occurred more than twice as often in the amoxicillin group than the erythromycin group . In each group, the number of patients failing to complete treatment was similar; the main reasons cited for discontinuation were gastrointestinal symptoms . The results indicate that both erythromycin ethylsuccinate and clavulanate-potentiated amoxicillin are well tolerated and are equally effective for routine empirical treatment of acute respiratory tract infections.

Can J Microbiol, 1989 Nov, 35(11), 1022 - 30
Influence of far-ultraviolet radiation on the permeability of the outer membrane of Escherichia coli; Mody R et al.; Far-ultraviolet radiation (254 nm) at a dose of 10, 20, and 30 J/m2 was found to disrupt the outer membrane permeability barrier of Escherichia coli to various antibiotics, dyes, and detergents . The degree of sensitization to these agents was proportional to the radiation dose . The irradiated cells showed a significant increase in the sensitivity of hydrophilic antibiotics (ampicillin, carbenicillin, penicillin), whereas much less sensitization was found towards hydrophobic probes (kanamycin, erythromycin, rifamycin SV, crystal violet, phenol, novobiocin) and detergents (dodecyl sulfate, bile salt, Triton X-100) . The biochemical data and ultrastructural analysis of the outer membrane by freeze-etching have shown that the increase in phospholipid:protein ratio after irradiation had changed the architecture of the outer membrane from a highly asymmetric bilayer structure with densely packed lipopolysaccharide--protein particles on the outer half, to one predominantly exhibiting smooth phospholipid bilayer characteristics . The structure, composition, and barrier function of the outer membrane were restored to normal within 3 h of postirradiation incubation in nonproliferative medium . During this period, the acquisition of resistance towards a hydrophilic antibiotic (ampicillin) was faster than that for a hydrophobic agent (phenol).

J Bacteriol, 1989 Nov, 171(11), 5872 - 81
Cloning of genes governing the deoxysugar portion of the erythromycin biosynthesis pathway in Saccharopolyspora erythraea (Streptomyces erythreus); Vara J et al.; Genes that govern the formation of deoxysugars or their attachment to erythronolide B and 3 alpha-mycarosyl erythronolide B, intermediates of the biosynthesis of the 14-membered macrolide antibiotic erythromycin, were cloned from Saccharopolyspora erythraea (formerly Streptomyces erythreus) . Segments of DNA that complement the eryB25, eryB26, eryB46, eryC1-60, and eryD24 mutations blocking the formation of erythronolide B or 3 alpha-mycarosyl erythronolide B, when cloned in Escherichia coli-Streptomyces shuttle cosmids or plasmid vectors that can transform S . erythraea, were located in a ca . 18-kilobase-pair region upstream of the erythromycin resistance (ermE) gene . The eryC1 gene lies just to the 5' side of ermE, and one (or possibly two) eryB gene is approximately 12 kilobase pairs farther upstream . Another eryB gene may be in the same region, while an additional eryB mutation appears to be located elsewhere . The eryD gene lies between the eryB and eryC1 genes and may regulate their function on the basis of the phenotype of an EryD- mutant.

Zhonghua Yi Xue Za Zhi (Taipei), 1989 Nov, 44(5), 336 - 40
Legionnaires' disease following cardiac transplantation; Wang RS et al.; One case of Legionnaires' disease in cardiac transplant recipient is reported . She was diagnosed by immunofluorescence study of bronchoscopic lavage specimen and was treated by oral erythromycin successfully . The main presentations are fever and single pulmonary nodule with rapid progression and cavitation . In the literatures report, two complicated Legionnaires' disease was reported in cardiac transplant recipient . This case is less complicated than reported and is the first case in this country.

Fam Med, 1989 Nov-Dec, 21(6), 425 - 7
The treatment of nonstreptococcal pharyngitis with erythromycin: a preliminary study; Marlow RA et al.; This preliminary study evaluated the effectiveness of enteric-coated erythromycin in the treatment of adults with nonstreptococcal pharyngitis . Twenty-six patients, aged 12 or older, with nonstreptococcal pharyngitis were randomly assigned in a double-blind fashion to receive either enteric-coated erythromycin or placebo for 10 days . Each day the patients rated the soreness of their throats and how sick they felt . The use of erythromycin appeared to decrease the median number of days for the feeling of sickness to improve (two days versus four days, P less than .01) as well as to decrease the median number of days for the feeling of sickness to resolve (three-and-a-half days versus five days, P less than .05) . This apparent improvement in sickness occurred even though there was no significant decrease in the soreness of the throat in patients treated with erythromycin compared to those patients treated with placebo . Treatment with enteric-coated erythromycin appeared to shorten the time until improvement in this group of adults with nonstreptococcal pharyngitis.

DICP, 1989 Nov, 23(11), 878 - 9
Carbamazepine toxicity precipitated by intravenous erythromycin; Mitsch RA; The ability of erythromycin to inhibit the hepatic metabolism of carbamazepine causes carbamazepine toxicity . The severity of this drug interaction has been proposed to be related to the dose of erythromycin . The introduction of oral erythromycin produces a two- to fourfold increase in the carbamazepine serum concentration and the resultant toxic manifestations . Carbamazepine toxicity and a more marked increase in carbamazepine serum concentration were observed in a patient treated with intravenous erythromycin.

J Bacteriol, 1989 Nov, 171(11), 6093 - 6
Calcium requirement for gliding motility in myxobacteria; Womack BJ et al.; The ability to glide on a solid surface was inducible by calcium ion in Stigmatella aurantiaca . The induction of motility but not motility itself was prevented by chloramphenicol and erythromycin . Calcium ion was also required for cells to glide, even when they were previously induced . The ability of Myxococcus xanthus to glide in groups using the S motility system but not as single cells (A system) was prevented by chloramphenicol and erythromycin.

J Mol Biol, 1989 Oct 20, 209(4), 655 - 65
Defining the structural requirements for a helix in 23 S ribosomal RNA that confers erythromycin resistance; Douthwaite S et al.; The helix spanning nucleotides 1198 to 1247 (helix 1200-1250) in Escherichia coli 23 S ribosomal RNA (rRNA) is functionally important in protein synthesis, and deletions in this region confer erythromycin resistance . In order to define the structural requirements for resistance, we have dissected this region using in vitro mutagenesis . Erythromycin resistance is established after a minimal deletion of three bases, CAU1231 or AUG1232 . The maximum deletion observed to confer resistance is 25 bases . The level of erythromycin resistance conferred by intermediate sized deletions is variable and some deletion mutants show a sensitive phenotype . Deletions that extend into the base-pairing between GCC1208 and GGU1240 result in non-functional 23 S RNAs, which consequently do not confer resistance . A number of phylogenetically conserved nucleotides have been shown to be non-essential for 23 S RNA function . However, removal of either these or non-conserved nucleotides from helix 1200-1250 measurably reduces the efficiency of 23 S RNA in forming functional ribosomes . We have used chemical probing and a modified primer extension method to investigate erythromycin binding to wild-type and resistant ribosomes with a 12-base deletion in 23 S RNA . Erythromycin interacts as strongly with mutant 23 S RNA as with wild-type 23 S RNA . Deletions in the 1200-1250 helix do not therefore confer resistance by reducing erythromycin binding, but by suppressing the effects of the drug at the level of its mechanism of action.

Schweiz Med Wochenschr, 1989 Oct 7, 119(40), 1372 - 4
{Pharmacodynamics of erythromycin lactobionate during tonsillectomy in children}; Leuthardt R et al.; In 22 children serum levels and concentration of erythromycin in the tonsil tissue after intravenous injection were measured . The concentration of erythromycin in the tonsils one hour after injection was four times the serum level . Two hours after injection the ratio was reduced significantly to 1.2 . From the results it is concluded that perioperative antibiotic therapy with erythromycin has pharmacodynamic advantages.

Ned Tijdschr Geneeskd, 1989 Oct 7, 133(40), 1990 - 2
{Another case of Hantaan virus infection in The Netherlands}; Lahaije JJ et al.; In a serological survey among Dutch patients suspected of leptospirosis, using a recently developed enzyme-linked immunosorbent assay, a patient was traced with a high antibody titre to Hantaan virus . No anti-leptospira antibodies were detected in this 27-year-old man . Shortly before he had been admitted to the hospital with progressive dyspnoea and coughing, accompanied with high fever . An interstitial pneumonia was diagnosed . He subsequently developed a progressive renal failure with proteinuria and polyuria . Later a liver failure accompanied with thrombocytopenia, anaemia and coagulation disturbances occurred . Before an aetiological diagnosis was made, the patient was treated with erythromycin . The patient eventually recovered completely . Based on the clinical symptoms and the positive serology, it was concluded that the disease diagnosed had probably been caused by a Hantaan virus infection . The diagnostic value of Hantaan virus serology in patients with similar symptoms is stressed.

Biochem Pharmacol, 1989 Oct 1, 38(19), 3179 - 84
Similarities and differences in the regulation of hepatic cytochrome P-450 enzymes by diabetes and fasting in male rats; Ma Q et al.; The effects of streptozotocin-induced diabetes and fasting on hepatic cytochrome P-450 enzymes in sexually mature male rats were studied by immunochemical techniques and enzyme assays . The level of cytochrome P-450ac (an acetone/ethanol inducible form), 65 pmol/mg microsomal protein in control rats, increased 4- to 5-fold in diabetic rats and 3- and 5-fold in fasting rats . In contrast, P-450 UT-A (a male specific form) decreased drastically from 295 pmol/mg in the control group to about 10% of this value in diabetic rats and to 50% in fasting rats . P-450 PCN-E (a 16 alpha-cyanopregnenolone/dexamethasone inducible form), on the other hand, decreased from 151 pmol/mg to 38% in diabetic rats and increased 2-fold in fasting rats . These changes were also reflected in catalytic activities using N-nitrosodimethylamine, benzphetamine, and erythromycin as substrates . Slight changes in cytochromes P-450 UT-F, P-450 UT-I and P-450 PB-C were also observed under these conditions, but the biological significance is not known . These results suggest that different mechanisms exist for the regulation of the expression of cytochrome P-450 enzymes in diabetic and fasting rats.

Toxicol Lett, 1989 Oct, 49(1), 61 - 8
Induction of the rat hepatic microsomal mixed-function oxidases by cimetidine; Ioannides C et al.; The ability of cimetidine to induce the hepatic microsomal mixed-function oxidases was investigated in rats treated orally with the drug at 3 dose levels: 10, 100 and 500 mg/kg . At the highest dose only, cimetidine stimulated the dealkylations of ethoxyresorufin, ethoxycoumarin and pentoxyresorufin but inhibited that of erythromycin and had no effect on the demethylation of dimethylnitrosamine . At the highest dose cimetidine had a small effect on the activation of Glu-P-1 to mutagens in the Ames test but induced proteins recognised in Western blots by antibodies to P450 I A1 and P450 II B1 . It is concluded that cimetidine is a weak selective inducer of cytochrome P-450 forms, but at therapeutic doses its inductive effect is most unlikely to be of any clinical or toxicological consequence.

Curr Genet, 1989 Oct, 16(4), 273 - 9
A single nucleotide substitution at the rib2 locus of the yeast mitochondrial gene for 21S rRNA confers resistance to erythromycin and cold-sensitive ribosome assembly; Cui Z et al.; We have studied a mutation (cs23) in the mitochondrial gene for 21S rRNA that affects the peptidyl transferase center of the ribosome and conditionally blocks the assembly of the 54S ribosomal subunit . Strains carrying this mutation are resistant to erythromycin and cold-sensitive for growth on nonfermentable carbon sources (Singh et al . 1978) Mitochondria isolated from mutant cells grown on glucose at 20 degrees C, the nonpermissive temperature, were depleted of the 54S subunit and instead contained a novel 45S ribosomal particle . After mutant cells were shifted from 20 degrees C to 32 degrees C, 54S subunits were assembled, apparently from the 45S particles and pre-existing ribosomal proteins . DNA sequencing revealed that the mutant phenotype is a consequence of a C to A transversion at position 3993 of the 21S rRNA gene . Previously, C to U and C to G mutations have been identified at the same position in the 21S rRNA sequence . This position corresponds to C-2611 in the E . coli 23S RNA, a nucleotide that appears to be conserved in the large rRNA of all erythromycin-sensitive ribosomes.

Avian Dis, 1989 Oct-Dec, 33(4), 631 - 5
Hemagglutination, hydrophobicity, enterotoxigenicity, and drug-resistance characteristics of avian Escherichia coli; Erganis O et al.; A total of 35 Escherichia coli isolates obtained from necropsy materials of hens with septicemia in the Konya region of Turkey were examined for hemagglutination (HA), cell-surface hydrophobicity, enterotoxigenicity, and drug resistance . HA tests were performed on live cultures with human (group A), bovine, avian (chicken), and guinea pig erythrocytes with and without mannose . Nine HA patterns were observed . Of the 35 isolates, 62.8% exhibited mannose sensitive hemagglutination (MSHA), 8.6% exhibited mannose resistant hemagglutination (MRHA), and 28.6% did not hemagglutinate . Of the isolates, 85.7% were hydrophobic by a salt aggregation test (SAT) . Only three isolates were enterotoxigenic by a suckling mouse assay . The majority of the isolates were resistant to chloramphenicol, tetracycline, streptomycin, ampicillin, erythromycin, and trimethoprim + sulfamethoxazole but were highly sensitive to gentamicin and nalidixic acid.

Can J Vet Res, 1989 Oct, 53(4), 385 - 9
A field evaluation of an indirect fluorescent antibody-based broodstock screening test used to control the vertical transmission of Renibacterium salmoninarium in Chinook salmon (Oncorhynchus tshawytscha); Armstrong RD et al.; Ovarian fluid samples from erythromycin treated and untreated spawning three year old Chinook salmon were screened independently by two laboratories for the presence of Renibacterium salmoninarum using the indirect fluorescent antibody technique (IFAT) . Agreement between the results of the two laboratories could be explained by chance when R . salmoninarum cell numbers as low as one per sample were considered sufficient to represent a positive result . If a positive result was considered to be the detection of larger numbers of R . salmoninarum cells (greater than 51 cells per sample), agreement increased and there was a statistically significant association between the results of the two laboratories . However, the level of agreement did not reach satisfactory levels for a population screening test . Furthermore, approximately 60% of the samples yielded false negative results when IFAT results were compared with positive culture results . These results led to the conclusion that the IFAT screening procedure, as carried out, was unsuitable for the purposes intended . Erythromycin injection of the spawning fish had no statistically significant effect on the results of the IFAT screening test.

Dtsch Tierarztl Wochenschr, 1989 Oct, 96(9), 449 - 51
{The compatibility of the new ionophore-coccidiostats with other chemotherapeutics in broilers}; Laczay P et al.; The compatibility of Salinomycin, Narasin or Maduramycin with Tiamulin, Erythromycin, Tylosin, Kitasamycin, Flumequine, Sulfachlorpyrazine or Sulfaquinoxaline was tested in cockerels in three experiments . It was found that Salinomycin and Narasin are incompatible with Tiamulin, Erythromycin, Sulfachlorpyrazine and Sulfaquinoxaline . The effect of incompatibility was shown more markedly with the administration of Salinomycin than with Narasin . Maduramycin was also shown as incompatible with Tiamulin although this interaction was nowhere near as severe as in the case of Salinomycin or Narasin . It caused a significant weight gain depression without mortality . Because of the significant weight gain depression, however, the administration of Tiamulin in the presence of Maduramycin in feed will not be recommended . At the same time, Maduramycin proved to be fully compatible with Erythromycin, Sulfachlorpyrazine and Sulfaquinoxaline . All three anticoccidials tested showed total compatibility with Tylosin, Kitasamycin and Flumequine.

Mol Microbiol, 1989 Oct, 3(10), 1405 - 14
Molecular characterization of a gene from Saccharopolyspora erythraea (Streptomyces erythraeus) which is involved in erythromycin biosynthesis; Dhillon N et al.; A 7.3 kbp DNA fragment, encompassing the erythromycin (Em) resistance gene (ermE) and a portion of the gene cluster encoding the biosynthetic genes for erythromycin biosynthesis in Saccharopolyspora erythraea (formerly Streptomyces erythraeus) has been cloned in Streptomyces lividans using the plasmid vector pIJ702, and its nucleotide sequence has been determined using a modified dideoxy chain-termination procedure . In particular, we have examined the region immediately 5' of the resistance determinant, where the tandem promoters for ermE overlap the promoters for a divergently transcribed coding sequence (ORF) . Disruption of this ORF using an integrational pIJ702-based plasmid vector gave mutants which were specifically blocked in erythromycin biosynthesis, and which accumulated 3-O-alpha-L-mycarosylerythronolide B: this behaviour is identical to that of previously described eryC1 mutants . The eryC1-gene product, a protein of subunit Mr 39,200, is therefore involved either as a structural or as a regulatory gene in the formation of the deoxyamino-sugar desosamine or in its attachment to the macrolide ring.

Br J Dermatol, 1989 Oct, 121(4), 497 - 502
A 4% erythromycin and zinc combination (Zineryt) versus 2% erythromycin (Eryderm) in acne vulgaris: a randomized, double-blind comparative study; Habbema L et al.; A double-blind, randomized multi-centre study was performed to evaluate the efficacy of a 4% erythromycin and zinc combination (Zineryt) versus 2% erythromycin (Eryderm) . One-hundred and twenty-two patients suffering from acne vulgaris were treated with either Zineryt lotion or 2% erythromycin lotion . Acne grading and lesion counts for comedones, papules, pustules, nodules and macules were performed at each visit at 0, 1, 2, 4, 8 and 12 weeks . Treatment with Zineryt lotion was found to be more effective than with 2% erythromycin as regards the reduction in number of the acne lesions and the severity grade of the acne.

Biochem Pharmacol, 1989 Oct 1, 38(19), 3341 - 5
Selective alteration of constitutive hepatic cytochrome P-450 enzymes in the rat during parenteral hyperalimentation; Knodell RG et al.; Decreased drug metabolism and hepatic cytochrome P-450 levels have been shown previously to occur in rats receiving total parenteral nutrition (TPN) compared to animals receiving the same hyperalimentation solution enterally (TEN) . In the present studies, animals received a 7-day infusion of a 25% glucose-2.75% crystalline amino acid solution via a catheter in the jugular vein or stomach; hepatic microsomal levels of four major constitutive cytochromes P-450 were determined subsequently by immunoquantitation and correlated with metabolism of selected substrates biotransformed by these enzymes . TPN resulted in a marked decrease in apoprotein of two constitutive cytochromes P-450, P-450UT-A and P-450PCN-E, compared to TEN experiments (for P-450UT-A, 11.0 +/- 1.8 vs 44.7 +/- 6.5% of total cytochrome P-450 measured by CO-difference spectra, P greater than 0.001; for P-450PCN-E, 15.4 +/- 4.4 vs 30.2 +/- 7.6%, P less than 0.01), but apoprotein levels of two other constitutive cytochromes P-450, P-450PB-C and P-450UT-F, showed relatively little change . Concordant reductions in metabolism of benzphetamine, ethylmorphine and erythromycin were seen in TPN animals . While the mechanisms responsible for these selective changes in the synthesis and function of individual cytochromes P-450 remain to be elucidated, altered gene transcription due to differences in portal blood composition elicited by intravenous versus enteral feeding is a possible hypothesis . These studies also provide information which should be valuable in designing studies to probe further the clinical question of whether TPN induces significant alterations in human drug metabolism.

Ned Tijdschr Geneeskd . 1989 Sep 30;133(39):1944.
{Interaction between erythromycin and carbamazepine}; Goldhoorn PB et al.; A six-month-old girl receiving erythromycin was given carbamazepine treatment . Two days later signs of carbamazepine intoxication developed and a serum carbamazepine concentration of 30 mg/l was found (4-9 mg/l being the desired therapeutical level) . The interaction of erythromycin and carbamazepine by liver enzyme competition is clinically significant.

Antimicrob Agents Chemother, 1989 Sep, 33(9), 1634 - 5
In vitro susceptibilities of Chlamydia pneumoniae (Chlamydia sp . strain TWAR); Chirgwin K et al.; The in vitro susceptibilities of two clinical isolates of Chlamydia pneumoniae from Brooklyn, N.Y., were determined for tetracycline, erythromycin, sulfamethoxazole, ciprofloxacin, and three new macrolides--azithromycin, clarithromycin, and roxithromycin . Clarithromycin was the most active drug tested, followed by the other macrolides, tetracycline, and ciprofloxacin.

Pharmacol Toxicol, 1989 Sep, 65(3), 198 - 203
The interaction between cyclosporin A and erythromycin studied by means of an isolated perfused rat liver model; Fabre I et al.; The isolated perfused rat liver model was successfully used to study the clinical interaction observed between cyclosporin A (CsA) and erythromycin (ER) . Three experimental studies were performed . In a "Control group", isolated rat livers were perfused with 60 micrograms 3H-CsA for 20 min . In an "ER group", isolated rat livers were simultaneously perfused with 60 micrograms 3H-CsA and 6.0 mg ER . In an "ER ind group", rats were treated with ER for 5 days, conditions under which the P450IIIA gene subfamily, principally involved in CsA metabolism, was specifically induced, and isolated rat livers were perfused with 60 micrograms 3H-CsA for 20 min . Biological parameters of the liver model such as biliary flow, oxygen consumption and pH were similar whatever group of animals . Biliary excretion of total radiolabel (sum of CsA and all the metabolites = CsAT) was similar in both the "Control" and "ER" groups but significantly higher in the "ER ind" group with respectively 8.05 +/- 0.81%, 8.45 +/- 1.93% and 14.54 +/- 2.12% of the entire amount of infused drug excreted during 2 hr . Using a high performance liquid chromatography method which specifically resolves unchanged CsA from its metabolites, we demonstrated that, although similar amounts of radiolabelled material were excreted in both the "Control" and "ER" groups, the CsA/metabolite ratio was lower than 1.0 in the "Control group" and higher than 1.0 in the "ER group", suggesting an inhibition of CsA metabolism by ER in the "ER group" . These data could explain the increase in CsA blood levels observed in the clinic following administration of high ER doses and the reversing effect when ER administration is stopped.

J Vet Pharmacol Ther, 1989 Sep, 12(3), 289 - 95
A comparison of the various routes of administration of erythromycin in cattle; Burrows GE et al.; A comparison of i.v., i.m . and s.c . administration erythromycin base in polyethylene glycol at 15 mg/kg and 30 mg/kg body weight was carried out in beef-type calves of approximately 200 kg body weight . Additional evaluations were carried out with oral administration of erythromycin phosphate and erythromycin stearate . Absorption of erythromycin was very slow by both the i.m . and s.c . routes of administration with a Kab of 0.0135 min-1 and 0.0185 min-1 for i.m . and 0.0032 min-1 and 0.0074 min-1 for s.c . at 15 mg/kg and 30 mg/kg, respectively . The bioavailability (32-42%) and peak serum concentrations were much lower with s.c . than with i.m . (60-65%) administration . The disposition of erythromycin administered i.v . appeared to be representative of dose-dependent kinetics rather than dose-independent first-order kinetics inasmuch as the elimination half-time (t1/2B) increased from 174.5 +/- 13 min for the 15 mg/kg dosage to 239 +/- 10.8 min with 30 mg/kg dosage . An acute apparent cardiovascular effect accompanied i.v . administration of erythromycin at 30 mg/kg dosage but not at 15 mg/kg . Severe diarrhea followed oral administration of either erythromycin phosphate or erythromycin stearate.

J Antimicrob Chemother, 1989 Sep, 24(3), 455 - 62
Erythromycin ethylsuccinate, base and acistrate in the treatment of upper respiratory tract infection: two comparative studies of tolerability; Saloranta P et al.; The efficacy and tolerability of erythromycin ethylsuccinate, erythromycin base and erythromycin acistrate were studied in two separate randomized studies in 80 and 82 primary health care patients with upper respiratory tract infections . In Study I, the patients were given either ethylsuccinate 666 mg tid or base 500 mg qid for ten days . Possible side-effects, abdominal pain, nausea, diarrhoea and vomiting, were recorded daily by the patient . Study II followed the same design as Study I with the exception of the side-effect evaluation method . Patients were given in a randomized fashion ethylsuccinate 666 mg tid, or acistrate 400 mg qid . Side-effect evaluation was based on a 10-cm analogue visual scale to record abdominal pain, while nausea, vomiting and diarrhoea were recorded as daily frequencies . These studies indicated that erythromycin ethylsuccinate caused significantly less abdominal pain than the base form (chi 2-test), but there were no significant differences in tolerance between the ethylsuccinate and acistrate forms . Other tolerance parameters revealed no real differences . The clinical response was good with all erythromycin preparations at the doses used in this study.

Am J Physiol, 1989 Sep, 257(3 Pt 1), G470 - 4
Erythromycin is a motilin receptor agonist; Peeters T et al.; Erythromycin A (EMA) is a potent stimulator of gastrointestinal motor activity . In vitro studies suggest that it mimics motilin, a peptide that stimulates motor activity in human and in rabbit via smooth muscle receptors . We have compared the in vitro contractile effect of EMA and two derivatives, 8,9-anhydro-EMA-6,9-hemiketal (EM201) and EMA N-oxide, on rabbit duodenal smooth-muscle strips with their ability to displace iodinated motilin bound to crude smooth-muscle membrane fractions . The concentrations required to induce 50% of the maximum contractile response to a supramaximal dose of acetylcholine were 5.0 x 10(-8), 2.0 x 10(-6), and 1.0 x 10(-4) M for, respectively, EM201, EMA, and EMA N-oxide . The concentrations required to displace 50% of the labeled motilin were, in the same order, 1.0 x 10(-8), 1.3 x 10(-7), and 4.0 x 10(-6) M . Both parameters were well correlated . The dose-response curve of the EMA was parallel to that of motilin and the effects of motilin and EMA were additive . Contractions induced by EMA were insensitive to pretreatment with tetrodotoxin or atropine . EMA had no effect on muscle strips of rat or dog duodenum but did induce contractions in human strips . EMA was totally ineffective on ileal preparations, which are also unresponsive to motilin and in which motilin binding is absent . EMA has therefore the same regional and species specificity as motilin . We conclude that EMA is a motilin receptor agonist.

J Invest Dermatol, 1989 Sep, 93(3), 349 - 52
Studies on the efficacy of methyl esters of n-alkyl fatty acids as penetration enhancers; Chukwumerije O et al.; The efficacy of the methyl esters of medium chain n-alkyl fatty acids as penetration enhancers was evaluated in vitro using various animal and human skins with minoxidil as the test drug . Both methyl nonanoate and methyl caprate at a 10% concentration were found to be effective penetration enhancers for a 2% solution of minoxidil in alcohol USP . The percent of the applied radioactive dose of minoxidil penetrated after 17 h was 5-8 times greater for methyl non-anoate and methyl caprate enhanced solutions than for a 2% solution of minoxidil in alcohol USP alone or with the addition of 10% Azone, dimethylsulfoxide (DMSO) or N,N-diethyl-m-toluamide (DEET) . The penetration enhancing activity of methyl caprate was effective for human, mouse, and hamster skins . Methyl caprate also enhanced the penetration of vitamin D3, erythromycin, triamcinolone acetonide, testosterone, and hydrocortisone.

Gastroenterology, 1989 Sep, 97(3), 751 - 5
Legionella infection of the colon presenting as acute attack of ulcerative colitis; Schmidt T et al.; A 42-yr-old woman with long-standing ulcerative colitis of the descending colon, sigmoid, and rectum presented with bloody diarrhea, tenesmus, and high fever . Endoscopic findings were compatible with an acute attack of ulcerative colitis, which proved to be resistant to systemic corticosteroid treatment . In the presence of an acute abdomen with ascites and double-contoured colonic wall, hemicolectomy was performed . Postoperatively, high temperature, hyponatremia, and elevated liver enzyme levels persisted . Pleural effusions developed . Antibodies to Legionella pneumophila serogroup 3 were detected in the serum . Erythromycin therapy induced rapid improvement . In a massive submucosal edema of the affected colon, L . pneumophila of the same serogroup was demonstrated by direct immunofluorescence staining.

Infect Immun, 1989 Sep, 57(9), 2872 - 7
Major integral membrane protein immunogens of Treponema pallidum are proteolipids; Chamberlain NR et al.; A number of the major pathogen-specific immunogens of Treponema pallidum were characterized recently as amphiphilic, integral membrane proteins by phase partitioning with Triton X-114 (J . D . Radolf, N . R . Chamberlain, A . Clausell, and M . V . Norgard . Infect . Immun . 56:490-498, 1988) . In the present study, we demonstrated that the same membrane immunogens (designated as detergent phase proteins {DPPs}) become radiolabeled upon in vitro incubation of T . pallidum with various 3H-labeled fatty acids . Radioimmunoprecipitation with a monoclonal antibody confirmed that the 3H-labeled 47-kilodalton protein corresponded to the well-characterized treponemal antigen with the identical apparent molecular mass . Failure to detect 3H-labeled DPPs following incubation with erythromycin confirmed that protein acylation required de novo protein synthesis by the bacteria . When treponemes were incubated with {3H}myristate, {3H}palmitate, or {3H}oleate, radiolabeled proteins corresponding to the DPPs were detected upon autoradiography . Demonstration that a number of the abundant membrane immunogens of T . pallidum are proteolipids provides information to help clarify their membrane association(s) and may serve to explain their extraordinary immunogenicity.

Plasmid, 1989 Sep, 22(2), 151 - 9
Involvement of a Spiroplasma citri plasmid in the erythromycin-resistance transfer; Salvado JC et al.; An erythromycin-resistant strain (M4 Er-1) was selected from Spiroplasma citri M4+ . The transfer by transformation of the erythromycin-resistance character to the erythromycin-sensitive S . citri strain R8A2+ was studied . Transfer became effective and reproducible when cells were treated with alkali cations plus polyethylene glycol . Comparison of the efficiency of transformation of the erythromycin-sensitive strain S . citri R8A2+ by total and extrachromosomal DNA purified from the erythromycin-resistant strain M4 Er-1 showed that the plasmid pM42 was able to transfer the erythromycin-resistance . pM42 was mapped with restriction endonucleases and found to be related to the pMH1 plasmid previously isolated from S . citri MH . Hybridization analysis of DNA from sensitive and resistant strains has shown that a sequence from pM42, analogous to a sequence from pMH1, was integrated at a specific locus in the chromosome of the erythromycin-resistant cells, i.e., of the transformed R8A2 cells and of the spontaneous mutant M4 Er-1 strain.

Biochem Pharmacol, 1989 Sep 1, 38(17), 2789 - 94
Effect of cannabidiol on cytochrome P-450 isozymes; Bornheim LM et al.; Cannabidiol (CBD) has been shown to inhibit mouse hepatic mixed-function oxidations of several drugs after acute treatment, whereas repetitive treatment resulted in the restoration of drug-metabolizing capabilities . We have found that acute CBD treatment modestly decreased cytochrome P-450 content but markedly decreased hexobarbital hydroxylase, erythromycin N-demethylase, and 6 beta-testosterone hydroxylase activities . Repetitive CBD treatment, on the other hand, resulted in the restoration of cytochrome P-450 content as well as hexobarbital hydroxylase and erythromycin N-demethylase activities . However, after such repeated treatments a fresh dose of CBD can once again inactivate erythromycin N-demethylase activity but not hexobarbital hydroxylase activity . The resistance of hexobarbital hydroxylase to re-inactivation by CBD was paralleled by stimulation of pentoxyresorufin O-dealkylase activity and the appearance of a 50 kD protein that was immunoreactive to an antibody raised against rat hepatic cytochrome P-450b . CBD metabolism in vitro by microsomes prepared from such CBD-"induced" animals, resulted in a pattern of metabolites different from that observed from comparable incubations with liver microsomes from either untreated or phenobarbital-treated animals . Thus, it appears that CBD initially inactivates at least one cytochrome P-450 isozyme, but after repetitive CBD treatment, an isozyme is induced that is resistant to further re-inactivation by CBD . This isozyme appears to be immunochemically similar to, but somewhat functionally distinct from, the isozyme induced by phenobarbital treatment in mice.

Antimicrob Agents Chemother, 1989 Sep, 33(9), 1531 - 4
In vitro and in vivo activities of clarithromycin against Mycobacterium avium; Fernandes PB et al.; There is no effective therapy to treat Mycobacterium avium complex infection in patients with acquired immune deficiency syndrome . Clarithromycin (A-56268; TE-031) is a new macrolide which is twofold more active than erythromycin against most aerobic bacteria . In addition, higher levels in serum and tissue are achieved with clarithromycin than with erythromycin . In this study, clarithromycin, erythromycin, difloxacin, temafloxacin, ciprofloxacin, rifampin, amikacin, and ethambutol were tested in vitro and in vivo against the M . avium complex . The MICs for 90% of strains tested were 4 micrograms/ml for clarithromycin, 64 micrograms/ml for erythromycin, 32 micrograms/ml for difloxacin, 8 micrograms/ml for temafloxacin, 4 micrograms/ml for ciprofloxacin, 4 micrograms/ml for rifampin, 32 micrograms/ml for amikacin, and 32 micrograms/ml for ethambutol . Beige mice were infected intravenously with 10(7) CFU of M . avium ATCC 25291 . Treatment was started on day 6 after infection and was administered twice a day at 8-h intervals for 9 days . Clarithromycin was the most effective compound in these tests and was effective in reducing the viable bacterial counts in the spleen when it was administered subcutaneously or orally at a dose of 25 mg/kg . Amikacin was the only other compound which showed activity in vivo . The peak concentration in serum at which clarithromycin was active was approximately 1.0 microgram/ml.

J Antimicrob Chemother, 1989 Sep, 24(3), 397 - 405
A new macrolide, TE-031 (A-56268), in treatment of experimental Legionnaires' disease; Kohno S et al.; The activity of a new macrolide, TE-031 (A-56268), against Legionella pneumophila in vitro was superior to the activities of roxithromycin, erythromycin and josamycin . The tissue concentrations of TE-031 in guinea pigs after oral administration (20 mg/kg) was much higher than those of roxithromycin, erythromycin and josamycin . The maximum concentration of TE-031 was 107.0 mg/kg in the lung, and 1.4 mg/l in the serum . The uptake of macrolides by cells collected by bronchoalveolar lavage in guinea pigs was measured by a radioisotopic method . The maximum ratios of intracellular to extracellular concentration of TE-031, roxithromycin, josamycin and erythromycin were 71.9, 24.8, 39.7 and 7.9, respectively . In infected guinea pigs, with the exception of erythromycin, the ratios were reduced to approximately half the values in normal animals . TE-031 showed greater therapeutic efficacy against experimental L . pneumophila pneumonia than roxithromycin, erythromycin and josamycin . TE-031 is a promising drug for treatment of legionella pneumonia and should be investigated in a clinical study on human Legionnaires' disease.

Infect Dis Clin North Am, 1989 Sep, 3(3), 653 - 64
New uses for old drugs; Abrutyn E; Existing therapies are often tried when new diseases are discovered or new manifestations of known organisms are recognized . This article reviews the successful application of older commonly used antibiotics to several representative "new" or "newly recognized" illnesses . Examples include new uses for the antistaphylococcal agents, penicillin, the tetracyclines, erythromycin, vancomycin, trimethoprim-sulfamethoxazole, pyrazinamide, metronidazole, clindamycin, and others.

J Pharmacol Exp Ther, 1989 Sep, 250(3), 1034 - 42
Suicide inactivation of cytochrome P-450 by methoxsalen . Evidence for the covalent binding of a reactive intermediate to the protein moiety; Labbe G et al.; Incubation of rat liver microsomes with {3H}methoxsalen and NADPH resulted in the covalent binding of a methoxsalen intermediate to proteins comigrating with cytochromes P-450 UT-A, PB-B/D, ISF-G and PCN-E . Binding was increased by pretreatments with phenobarbital, beta-naphthoflavone (beta NF) and dexamethasone . Such pretreatments also increased the loss of CO-binding capacity either after administration of methoxsalen, or after incubation of hepatic microsomes with methoxsalen and NADPH . Immunoprecipitation of the methoxsalen metabolite-protein adducts in phenobarbital-induced microsomes was moderate with anti-UT-A antibodies, but marked with anti-PB-B/D and anti-PCN-E antibodies . Immunoprecipitation was observed also with anti-ISF-G (anti-beta NF-B) antibodies in beta NF-induced microsomes . Methoxsalen (0.25 mM) inhibited markedly the benzphetamine demethylase activity of phenobarbital-induced microsomes and the erythromycin demethylase activity of dexamethasone-induced microsomes . Whereas methoxsalen itself did not produce any binding spectrum, in contrast either in vivo administration of methoxsalen or incubation in vitro with methoxsalen and NADPH resulted in a low-to-high spin conversion of cytochrome P-450 as suggested by the appearance of a spectrum analogous to a type I binding spectrum . This low-to-high spin conversion was apparently due to a methoxsalen intermediate (probably, covalently bound to the protein and preventing partial sixth ligation of the iron) . We conclude that suicide inactivation of cytochrome P-450 by methoxsalen is related to the covalent binding of a methoxsalen intermediate to the protein moiety of several cytochrome P-450 isoenzymes (including UT-A, PB-B/D, PCN-E as well as ISF-G and/or beta NF-B).

J Med Chem, 1989 Sep, 32(9), 2200 - 4
Synthesis and biological activity of photoactive derivatives of erythromycin; Arevalo MA et al.; Five photoactive derivatives of erythromycin have been synthesized by linking to 9(S)-aminoerythromycin either an aryl azide or a p-nitrophenyl ether . One derivative is an amide formed by reaction with (5-azido-2-formyl-phenoxy)acetic acid . Three derivatives are also amides, synthesized with 4-(p-nitroguaiacoxy)butanoic acid as a photoreactive group either directly or by interposing an amino acid (glycine or tyrosine) . The last derivative is the product of the aldehyde condensation of aminoerythromycin with 10-(p-nitroguaiacoxy)decanal . Two of these derivatives can easily be made radioactive for affinity labeling studies either by reduction with {3H}borohydride (aryl azide derivative) or by 125I iodination (4-(p-nitroguaiacoxy)tyrosyl derivative) . Although affected to different extents, the five erythromycin derivatives are biologically active and bind to the erythromycin-specific site on the bacterial ribosomes . In addition, the introduction of these groups changes the erythromycin inhibition pattern of peptide bond model reactions.

Ann Ig, 1989 Sep-Oct, 1(5), 1087 - 118
{Chlamydiae . 2 . Chlamydia trachomatis}; Del Piano M et al.; The Chlamydia trachomatis (C.t.) causes trachoma, inclusion conjunctivitis, lymphogranuloma venereum and it is the more frequent responsible of sexually transmitted infections; in fact, only in the United States, 3-4 million of people suffer from these infections each year . Besides, there are many secondary infections that may cause sterility in man and woman . Risk factors, for venereal infections owed to C.t., are related to the number of sexual partners, age, socioeconomics status and sexual preference . More frequently, the C.t . infects persons that begin sexual activity earlier, those who have many sexual partners and an higher level of education . The direct diagnosis for detecting C.t . can be performed with the citologic test, cell culture, direct immunofluorescence and enzyme immuno-assay . Although, the cell culture is the technique of choice, at present the immunofluorescence and enzyme immuno-assay are the methods preferred because of rapidity and esecution . The indirect diagnosis can be achieved by the complement fixation, indirect immunofluorescence and enzyme immuno-assay tests . In this case, excluding the complement fixation test not more reliable, the method of choice depends, above all, upon the kind of infection in progress . Tetracycline, erythromycin, rifampicin and cloramphenicol are considered the treatment of choice.

N Engl J Med, 1989 Aug 31, 321(9), 569 - 74
Acute eosinophilic pneumonia as a reversible cause of noninfectious respiratory failure; Allen JN et al.; Although chronic eosinophilic pneumonia is a well-known disorder, acute eosinophilic pneumonia has not been as well characterized . We describe the clinical features, results of bronchoalveolar lavage, and follow-up studies of four patients with acute eosinophilic pneumonia . The patients presented with an acute febrile illness, severe hypoxemia (partial pressure of arterial oxygen less than 60 mm Hg), diffuse pulmonary infiltrates, an increased number of eosinophils (mean +/- SEM, 42 +/- 4.8 percent) in bronchoalveolar-lavage fluid, and an absence of infection and previous atopic illness . The illness resolved rapidly after treatment with erythromycin and corticosteroids . The patients received doses of oral prednisone that were tapered over 10 days to 12 weeks, and none have relapsed since the steroids were discontinued . After a minimum follow-up period of five months, clinical evaluation, chest radiography, and pulmonary-function tests have shown no residual abnormalities attributable to the acute eosinophilic pneumonia . Follow-up bronchoalveolar lavage has demonstrated less than or equal to 1 percent eosinophils in all patients . We believe that we are describing an acute form of eosinophilic lung disease distinct from previously described syndromes . It can be diagnosed by bronchoalveolar lavage and seems to respond to treatment with corticosteroids.

Dtsch Med Wochenschr, 1989 Aug 18, 114(33), 1242 - 4
{An unusual course of thoracic actinomycosis}; Bross-Bach U et al.; A 56-year-old farmer who had been suffering from exogenous allergic alveolitis developed, after a long prodromal period of illness, a granulocyte-rich pericardial effusion and bilateral pleural effusions in which Actinomyces aggregates were identified . Despite intensive treatment with clindamycin, erythromycin and tetracycline (he was allergic to penicillin) he died in septic shock.

Genitourin Med, 1989 Aug, 65(4), 239 - 43
Primary and secondary syphilis, 20 years' experience . 3: Diagnosis, treatment, and follow up; Anderson J et al.; The methods of diagnosis (dark ground microscopy and serology), treatment, and follow up of 946 patients with primary and 854 with secondary syphilis who presented to a London STD clinic between 1965 and 1984 were reviewed retrospectively . On dark ground microscopy spirochaetes typical of Treponema pallidum were seen in 673 (78%) of 884 patients with primary syphilitic chancres . Of the patients with primary syphilis, 137 (14.5%) had negative serology results at presentation . Eight (0.9%) of the patients with secondary syphilis had negative results at presentation, but seven of these gave positive results one month later . Procaine penicillin was the treatment used most, and erythromycin the commonest alternative . The Jarisch-Herxheimer reaction occurred more often after treatment with penicillin than with erythromycin or tetracycline (p less than 0.005) . In most patients the Venereal Diseases Research Laboratory (VDRL) test showed a consistent fall in titre after treatment; a small proportion, however, continued to give positive results (some at a high titre) with no other evidence of reinfection or treatment failure.

J Pharm Sci, 1989 Aug, 78(8), 635 - 8
Variability in the absorption and disposition of erythromycin estolate in humans; Stubbs C et al.; The inter- and intrapersonal variability in the absorption and disposition of erythromycin estolate in humans was assessed by comparing total erythromycin serum concentrations in five subjects who each received a single erythromycin estolate tablet on three separate occasions under identical experimental conditions . Coefficients of variation for the pharmacokinetic parameters Cmax, Tmax, AUC0-12, MRT, and t1/2 were of a similar magnitude when calculated between subjects in any one administration phase or between phases . In addition, serum concentrations of both erythromycin base (active component) and erythromycin propionate were selectively determined in the same subjects only during the final two phases of the study . Comparison of AUC0-12 values showed that the percentage of the total area (base and ester components) present as erythromycin base remained relatively constant between administrations (mean values of 14.5 and 11.2%), with low coefficients of variation between subjects (10.8 and 11.6%) . Discrepancy value calculations revealed that the variability in serum concentration-time profiles between the three phases of the study fell into the "small"-to-"moderate" classification . From these data it is apparent that intrapersonal variations in the absorption and disposition of erythromycin estolate are of a similar magnitude to interpersonal variations and should be borne in mind in the design and interpretation of comparative bioavailability studies involving similar formulations of this compound . The relative proportions of erythromycin base and propionate did, however, remain fairly constant both between treatments and between subjects.

Pediatr Infect Dis J, 1989 Aug, 8(8), 491 - 5
Failure of erythromycin ointment for postnatal ocular prophylaxis of chlamydial conjunctivitis; Black-Payne C et al.; Chlamydia trachomatis is the most common pathogen associated with conjunctivitis during early infancy in the United States . During a 13-month interval at our medical center 4834 infants were born, 311 of whom (6.4%) had conjunctival specimens tested for chlamydial antigen before the age of 12 weeks . In 44 (14% of all tested infants, 0.9% of live births) chlamydial antigen was present . Because the rate of asymptomatic maternal chlamydial endocervical colonization is estimated to be 26% at our institution (previous prospective study), we calculated a minimal failure rate for erythromycin ocular prophylaxis of from 7 to 19.5% . A subsequent case-control study revealed that mothers of infants with chlamydial conjunctivitis were more likely to be primiparous (P = 0.03) and experience longer duration of rupture of membranes before delivery (P = 0.046) . We conclude that a substantial percentage of infants exposed to Chlamydia develop chlamydial conjunctivitis despite receiving erythromycin ocular prophylaxis.

Toxicology, 1989 Aug, 57(3), 267 - 86
Protective effect of flavonoids on drug-induced hepatotoxicity in vitro; Davila JC et al.; Primary cell cultures of neonatal hepatocytes were used to examine the protective effect of flavonoids in the presence of hepatotoxins . Catechin (CAT) and silybin (SIL) protected the hepatocytes against cell injury produced by erythromycin estolate (EE), amitriptyline (AT), nortriptyline (NT), and tert-butylhydroperoxide (TBOOH) . Leakage of lactate dehydrogenase (LDH), aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as morphological parameters, were used as indices of hepatotoxicity . Hepatocytes were exposed to EE (1 X 10(-4) M and 2 X 10(-4) M), AT, NT, and TBOOH (1 X 10(-4) M and 1 X 10(-3) M) for a 2-h period . These hepatotoxins caused significant LDH, AST, and ALT leakage (P less than 0.05) when compared to untreated control groups . NT was less toxic than its parent compound, AT . Changes in morphology were evident after 1 h of treatment with the toxicants, including: vacuole formation, size deformation and cell necrosis . As the concentration of hepatotoxins was increased, the changes were more pronounced . Pretreatment of the cultures with either CAT or SIL resulted in less enzyme leakage and morphological alterations by the hepatotoxins . The results of this study suggest that CAT and SIL may act by stabilizing the plasma membrane against toxic insult.

Nihon Kyobu Shikkan Gakkai Zasshi, 1989 Aug, 27(8), 980 - 3
{A case of the bare lymphocyte syndrome with clinical manifestations of diffuse panbronchiolitis}; Sugiyama Y et al.; Touraine et al reported some cases lacking HLA-class I antigens on the cell surface of their lymphocytes as "Bare lymphocyte syndrome" (BLS) . Recently we experienced a case of BLS the clinical features of which are very similar to those of diffuse panbronchiolitis (DPB) . Namely, she had chronic pansinusitis, diffuse nodular shadows on her chest X-ray film, obstructive impairment of pulmonary function tests and continuous increase of cold hemagglutinin titer . The pathogenesis of DPB is not confirmed . However, this case and other cases with sino-bronchial syndrome suggest that patients with DPB may have some immunodeficiencies . In addition the immunosuppressive action of erythromycin and its effectiveness on DPB were interesting . From these points of view, we discussed the relationship between this case and DPB, and the pathogenesis of DPB.

Nihon Kyobu Shikkan Gakkai Zasshi, 1989 Aug, 27(8), 960 - 7
{Two cases of Mycoplasma pneumoniae pneumonia with obstructive ventilatory disturbance}; Aoshima M et al.; Mycoplasma pneumoniae (M . pneumoniae) pneumonia is usually considered as a benign disease, but in rare cases, the disease is fatal . Fatal cases requiring mechanical ventilation and many extrapulmonary complications have been reported . Cases accompanied with obliterative bronchiolitis also have been reported . Two cases of M . pneumoniae pneumonia with obstructive ventilatory disturbance were reported . In both cases clinical diagnosis of M . pneumoniae pneumonia was confirmed by a rise in the complement fixation antibody titer, a rise of the cold hemagglutinin titer and isolation of M . pneumoniae from sputum and pharynx . In one case we performed transbronchial lung biopsy (TBLB) . The lung biopsy specimen showed bronchiolitis, so histological findings were thought to be compatible with ventilatory function . In both cases arterial oxygen pressure (PaO2) was below 60 Torr, by administration of erythromycin (EM) and adrenocorticosteroids, chest X-ray findings, atrial blood gas analysis findings and ventilatory function were improved.

J Pharmacol Exp Ther, 1989 Aug, 250(2), 746 - 51
Effects of clarithromycin on cytochrome P-450 . Comparison with other macrolides; Tinel M et al.; Repeated administration of clarithromycin (0.5 mmol.kg-1 p.o . daily for 5 days) to rats increased markedly the same cytochrome P-450 isoenzyme (P-450p) as that induced by troleandomycin . Clarithromycin, however, did not form cytochrome P-450 Fe(II)-metabolite complexes in vitro with microsomes from clarithromycin-treated rats or in vivo after repeated doses of clarithromycin . Nevertheless, clarithromycin formed cytochrome P-450 Fe(II)-metabolite complexes with microsomes from dexamethasone-treated rats in vitro, or after administration to dexamethasone-treated rats in vivo . Similar effects were observed with roxithromycin . In contrast, erythromycin and troleandomycin formed metabolic complexes when given alone, whereas josamycin, midecamycin and spiramycin did not form complexes, even in dexamethasone-treated rats . We conclude that clarithromycin and roxithromycin induce cytochrome P-450p, but do not form complexes with this isoenzyme, although they do form complexes with other glucocorticoid-inducible isoenzymes . We propose that macrolides may be classified into three groups, those forming complexes when given alone (e.g., erythromycin and troleandomycin), those forming complexes only in glucocorticoid-pretreated rats (clarithromycin and roxithromycin) and those not forming complexes (josamycin, midecamycin and spiramycin).

Kansenshogaku Zasshi, 1989 Aug, 63(8), 811 - 5
{The effect of erythromycin treatment on natural killer (NK) cell activity in patients with chronic lower respiratory tract infections}; Mikasa K et al.; We measured NK activity before and after administration of erythromycin in 7 cases of chronic respiratory infection, and investigated the relationship between NK activity and improvement of the clinical syndrome . 1) We saw a significant rise in NK activity after treatment of erythromycin . Values before and after ranged from 40.0 +/- 21/2% to 62.0 +/- 32.7% . 2) There was no correlation between treatment period of erythromycin and the rate of rise in NK activity in the various cases such as rapidly rising cases or slowly rising cases, etc . 3) We saw a rise in NK activity before improvement of the clinical syndrome . Therefore it is suggested that treatment of erythromycin affects a rise in NK activity.

Enferm Infecc Microbiol Clin, 1989 Aug-Sep, 7(7), 374 - 6
{Effect of erythromycin and phosphomycin on the ingestion and destruction capacity of the human polymorphonuclear leukocyte}; Amurrio C et al.; The aim of the present study was to evaluate the uptake and intracellular destruction capacity of the human neutrophil . Human neutrophils from healthy individuals not receiving any therapy were incubated during 15, 90 and 180 minutes with the minimal, intermediate and maximal doses achieved in serum during treatment with therapeutic doses of these antibiotics (3, 6.45 and 9.9 micrograms/ml of erythromycin and 30, 45 and 60 micrograms/ml of phosphomycin) . After this incubation, the uptake capacity and the intracellular destruction capacity of Candida guillermondii by neutrophils was assessed . Both erythromycin and phosphomycin maintained the baseline levels of both capacities in all the incubations evaluated . In addition, during the incubation with maximal dose erythromycin (15 min) a stimulatory tendency of the uptake and intracellular destruction capacity was observed.

Antimicrob Agents Chemother, 1989 Aug, 33(8), 1354 - 7
Purification and characterization of macrolide 2'-phosphotransferase from a strain of Escherichia coli that is highly resistant to erythromycin; O'Hara K et al.; Macrolide 2'-phosphotransferase {MPH(2')} was purified 90-fold from an erythromycin-resistant strain of Escherichia coli, and its enzymatic properties were investigated . MPH(2') is an inducible intracellular enzyme which showed high levels of activity with 14-member-ring macrolides and extremely low levels with 16-member-ring macrolides . The optimum pH for inactivation of oleandomycin was 8.2, and the optimum temperature of the reaction was 40 degrees C . Enzyme activity was lost by heat treatment at 50 degrees C for 1 min . The isoelectric point and molecular weight of the enzyme were 5.3 and 34,000, respectively . Purine nucleotides, such as GTP, ITP, and ATP, were effective as cofactors in the inactivation of macrolides . Iodine, EDTA, or divalent cations inhibited MPH(2') activity.

Paediatr Perinat Epidemiol, 1989 Jul, 3(3), 268 - 77
Chlamydia trachomatis infection in late pregnancy: a prospective study; Preece PM et al.; During a 1-year period, 3309 women were screened in pregnancy for Chlamydia trachomatis infection . A cervical swab was taken and chlamydial antigen was detected, using a monoclonal antibody ELISA technique, in 198 women (6%) . The prevalence of chlamydial infection was high in women under 20 years (14.5%), single women (14.2%) and black women (16.8%) . Binomial regression of these data estimates a relative risk of 2.9 for women under 20 years compared with women aged 25 and over . There was an interaction between race and marital status with a high risk in single white and single asian women (2.3, 4.5 respectively) but a similar risk in black single and black married women (3.0, 4.0 respectively) . Parity and social class did not effect the prevalence of antigen carriage . There was no demonstrable effect of maternal antigen carriage on outcome of pregnancy, gestation or admission to neonatal unit . Infants of 174 antigen-positive mothers were followed-up . Tissue culture for Chlamydia trachomatis was positive in 43 (24%) infants . Complications occurred in 23 (53%): 17 had conjunctivitis, three had lower respiratory tract infection and three both complications . Amongst 131 chlamydia-negative infants, complications occurred in 21 (16%) . Since this infection, in infants, responds promptly to erythromycin therapy, screening and treatment in pregnancy will convey little benefit in prevention of perinatal morbidity or perinatal mortality.

J Pediatr, 1989 Jul, 115(1), 46 - 50
Nosocomial legionnaires disease in a children's hospital; Brady MT; Between August 1982 and December 1985, seven patients at a children's hospital developed hospital-acquired pneumonia caused by Legionella pneumophila . Demographic data included the following: mean age 12.3 years (range 9 months to 20.5 years); male/female ratio 5:2; all patients were white . Some previously identified risk factors present in our patients included high-dose corticosteroid therapy (five patients), other immunosuppressive therapy (four), and chronic lung (five) or kidney (three) disease . Symptoms and signs included rapid onset, fever, cough, pleuritic chest pain, dyspnea, abdominal pain, diarrhea, and headache . Rhinitis, myalgia, and neurologic abnormalities were not noted . Chest roentgenograms revealed single-lobe consolidation in three patients, diffuse bilateral alveolar infiltrates in three, and pleural effusion in three . All patients were treated with erythromycin; three patients also received rifampin . Tracheal intubation and mechanical ventilation were required by four patients . Six patients improved after therapy . One child died of persistent lung disease 1 month after the onset of legionnaires disease . L . pneumophila was isolated from potable water in the hospital . Aerosol equipment cleansed with tap water and the showers were implicated as means of exposure by patients to contaminated potable water . No new nosocomial cases were seen after immunocompromised children were prohibited from taking showers, and sterile water was used to cleanse equipment for administering aerosol medications.

Biochem Pharmacol, 1989 Jul 1, 38(13), 2061 - 8
In vitro interaction of rat liver cytochromes P-450 with erythromycin, oleandomycin and erythralosamine derivatives . Importance of structural factors; Sartori E et al.; Several derivatives of the erythromycin, erythralosamine and oleandomycin series have been prepared . Their abilities to bind to rat liver microsomal cytochrome P-450 and to lead to the formation of stable 456 nm absorbing cytochrome P-450-metabolite complexes after their oxidative microsomal metabolism in vitro have been compared . The obtained data confirmed that cytochrome P-450 induced in rats either by macrolides or by 16 alpha-pregnenolone carbonitrile were the major isozymes involved in the binding of macrolides to liver microsomes and in metabolite-complex formation . They showed that (i) hydrophobicity was in general a beneficial factor for these two properties, (ii) the presence of a bulky substituent in position 3 of erythromycin dramatically decreased their affinity for these isozymes, and (iii) the simultaneous presence of bulky substituents in position 2' and 3 prevented iron-metabolite complex formation . These results led to the selection of two compounds, erythralosamine-2'-benzoate and erythralosamine-2',3-diacetate, which exhibited a particularly high affinity for macrolide inducible cytochrome P-450 and were very good precursors of cytochrome P-450-iron-metabolite complex formation.

Postgrad Med, 1989 Jul, 86(1), 55 - 9, 63
Using erythromycin . Some helpful observations; Latare PA et al.; Erythromycin is a very safe antibiotic that is effective against a wide variety of common and uncommon bacterial infections . Several formulations are available, each with a different absorption rate and dosing profile . The most common side effect of erythromycin is gastrointestinal intolerance, which appears to be related to disruption of intestinal motility . Gastrointestinal tolerance may be improved by limiting daily doses to less than 4 g; temporarily decreasing the total daily dose; using small doses of liquid suspension every 2, 3, or 4 hours; taking the medication with milk or food; and drinking water every 15 minutes two or three times after each dose . These measures may, in turn, improve compliance and efficacy in affected patients.

Acta Trop, 1989 Jul, 46(4), 209 - 12
Delay in emergence of mefloquine resistance in Plasmodium berghei by use of drug combinations; Puri SK et al.; Blood induced Plasmodium berghei infection in Swiss mice was exposed during successive passages to melfloquine alone or melfoquine in combination with dapsone or primaquine or erythromycin, and the level of resistance to melfoquine in four sub-lines was compared at ED90 level . Treatment with mefloquine alone resulted in a 201.14 fold increase in resistance after 21 passages . Use of drug combination (melfoquine + dapsone) delayed the acquisition of resistance as shown by a marginal increase of ED90 by 5.76 fold after 34 passages . Similarly, there was a 17.84 fold increase of resistance after 32 passages involving exposure to mefloquine-primaquine and a 112.28 fold increase after exposure to melfoquine-erythromycin combination for 31 passages . The study emphasizes that rational drug combinations should be developed to protect the melfoquine against the emergence of resistance in P . falciparum cases.

Eur J Clin Microbiol Infect Dis, 1989 Jul, 8(7), 653 - 4
Activity of new macrolides against Bordetella pertussis and Bordetella parapertussis; Hoppe JE et al.; MICs and MBCs of four new macrolides (azithromycin, clarithromycin, dirithromycin and roxithromycin) and two older macrolides (erythromycin and josamycin) for Bordetella pertussis and Bordetella parapertussis were determined . The activity of the new macrolides was as good as that of erythromycin, while josamycin was slightly less active . Bordetella parapertussis was more resistant than Bordetella pertussis.

Infection, 1989 Jul-Aug, 17(4), 227 - 31
Comparison of erythromycin ethylsuccinate and co-trimoxazole for treatment of pertussis; Hoppe JE et al.; Fifty-five ambulatory children with early culture-proven pertussis were treated for two weeks either with erythromycin ethylsuccinate (n = 28) (50-80 mg/kg/day in three doses during meals) or with co-trimoxazole (n = 27) (6-10 mg trimethoprim/kg/day in two doses after meals) . After completion of treatment, all patients in the erythromycin group were culture-negative, while in the co-trimoxazole group one child was still culture-positive . In this case vomiting may have played a role . Both agents appear to be able to eradicate Bordetella pertussis from the nasopharynx of patients with early whooping cough.

Clin Pharmacol Ther, 1989 Jul, 46(1), 99 - 102
Inhibition of alfentanil metabolism by erythromycin; Bartkowski RR et al.; To investigate a possible connection between erythromycin administration and reduced elimination of alfentanil, a controlled crossover study of alfentanil pharmacokinetics was undertaken . Six subjects were monitored for alfentanil plasma levels for 8 hours after alfentanil was administered . These measurements were obtained after a 0-, 1-, and 7-day course of erythromycin . Elimination half-life increased significantly (p less than 0.01) after 7 days from the control value of 84.0 +/- 8.2 minutes to 131.4 +/- 43.5 minutes . Clearance was decreased significantly (p less than 0.05) from 3.9 +/- 0.8 ml/kg/min to 2.9 +/- 1.2 ml/kg/min after 7 days . Values after 1 day were intermediate . Distribution volume did not change significantly . Subjects differed sharply in their sensitivity to erythromycin . Because of the interaction between erythromycin and alfentanil, we recommend that patients who are receiving erythromycin should be given alfentanil in reduced amounts or should avoid the drug completely.

Med Clin (Barc), 1989 Jun 24, 93(4), 125 - 8
{Nosocomial legionellosis: study of 51 cases}; Aguilar Bargallo X et al.; We report the features of 51 cases of hospital-acquired Legionella pneumophila pneumonia (HLP), diagnosed in our hospital during a period of about 5 years . Mean age was 64.6 years, and the male:female ratio 1.6 . 29% of HLP involved patients who were not admitted to the hospital at the time of diagnosis . The monthly distribution showed a maximal incidence in July and August . Only 6% of cases involved patients without underlying diseases . The most common underlying diseases were chronic obstructive lung disease (COLD) (37%), heart disease (29%) and immunosuppressant therapy (29%) . 21% of the patients with renal transplant had HLP . The only constant clinical feature was fever of 37.8 degrees C or higher . During the first 24-48 hours of illness, respiratory symptoms were not present in 41% of cases, and thoracic abnormalities in the physical examination were not present in 31% . The laboratory abnormalities were nonspecific and with incidence rates lower than 50% . In 41% of patients there was hypoxemia (60 mmHg or lower) with FiO2 of 0.21 . The most common radiological finding was the initial unilateral and unilobar involvement . Pleural effusion and cavitation developed in 20% and 4%, respectively . Overall mortality rate was 12% . In the 43 patients treated early with intravenous erythromycin, mortality rate was 7% . We think that the relatively low incidence of severe underlying immunosuppression and the inclusion of hospital-acquired pneumonia in our institution influenced the low mortality rate of the present study, in contrast with other series of hospital-acquired legionellosis.

Arch Biochem Biophys, 1989 Jun, 271(2), 284 - 99
Characterization of a phenobarbital-inducible dog liver cytochrome P450 structurally related to rat and human enzymes of the P450IIIA (steroid-inducible) gene subfamily; Ciaccio PJ et al.; A cytochrome P450 called PBD-1 isolated from liver microsomes of an adult male Beagle dog treated with phenobarbital (PB) is structurally and functionally similar to members of the P450IIIA gene subfamily in rat and human liver microsomes . The sequence of the first 28 amino-terminal residues of PBD-1 is identical in 15 and 20 positions, respectively, to the P450IIIA forms P450p from rat and P450NF (and HLp) from human . Upon immunoblot analysis, anti-PBD-1 IgG recognizes PCNa (P450p) and PCNb (PB/PCN-E) from rat, P450NF from human, and two proteins in liver microsomes from both untreated and PB-treated dogs . Similarly, anti-PCNb IgG cross-reacts with PBD-1 and with at least one protein in microsomes from untreated dogs and two proteins in microsomes from PB-treated dogs . P450IIIA-form marker steroid 6 beta-hydroxylase activities increase 2.5-fold upon PB-treatment of dogs and are selectively inhibited by anti-PBD-1 IgG . NADPH-dependent triacetyloleandomycin (TAO) complex formation and erythromycin demethylase, also marker activities for P450IIIA forms from rats and humans, increase 4- and 5-fold in dog liver microsomes upon PB treatment, whereas immunochemically reactive PBD-1 is induced 3-fold . In microsomes from PB-treated dogs, 5 mg anti-PBD-1 IgG/nmol P450 inhibits greater than 75 and 50% of TAO complex formation and erythromycin demethylase activity, respectively . TAO complex formation is not inhibited by chloramphenicol, a selective inhibitor of the major PB-inducible dog liver cytochrome P450, PBD-2 . These data suggest that PBD-1 or another immunochemically related form is responsible for a major portion of macrolide antibiotic metabolism by microsomes from PB-treated dogs and for steroid 6 beta-hydroxylation by microsomes from both untreated and PB-treated dogs . Major species differences were noted, however, in the apparent Km for 6 beta-hydroxylation of androstenedione by liver microsomes from untreated rats (24 microM), humans (380 microM), and untreated dogs (4700 microM).

Can J Physiol Pharmacol, 1989 Jun, 67(6), 582 - 6
The interaction between carbamazepine and erythromycin; Turner PV et al.; Erythromycin has been reported to interact with the anticonvulsant, carbamazepine, in both children and adults . Toxic serum levels of carbamazepine are observed within 24 h of antibiotic administration, suggesting a mechanism not previously described for other erythromycin-based drug interactions . In rats erythromycin significantly depressed the elimination of carbamazepine in animals induced with carbamazepine for 4 days but had no effect on carbamazepine elimination in noninduced animals . Although the in vitro metabolism of carbamazepine to its epoxide by hepatic microsomes prepared from noninduced rats was significantly inhibited by erythromycin, the inhibition of carbamazepine epoxidation was greatly enhanced in carbamazepine-induced rats . In the pig the sensitivity of carbamazepine metabolism to erythromycin was much greater than in the rat, indicating the existence of a large species difference in this particular drug interaction . It is concluded that the interaction between erythromycin and carbamazepine is caused by a direct inhibition of carbamazepine oxidation by the antibiotic.

Sci China B, 1989 Jun, 32(6), 661 - 70
Studies on response characteristics of drug ise's . (III)--Erythromycin electrodes and their selectivity toward quaternary ammoniums; Yao SZ et al.; Erythromycin sensitive electrodes have been proposed . Their selectivity toward quaternary ammoniums is described in terms of induction effect and steric hindrance effect: logKij = a1I-a2Z/R + a0, where I is induction effect index, a1, a2 and a0 are coefficients which depend on the electro-active material . A general formula has been suggested to relate the electrode selectivity to the carbon atom number (n) of the alkyl of the quaternary ammonium; logKij = A/2.7n-B/(0.80+1.26n)+C, where A, B and C are coefficients which depend on the electro-active material . logKij tends to a limited value C when n increases.

Neth J Med, 1989 Jun, 34(5-6), 306 - 9
Haemolytic anaemia due to cold agglutinins caused by psittacosis; Timmerman R et al.; A 69-yr-old previously healthy woman, presenting with jaundice and the clinical symptoms of an atypical pneumonia, was hospitalized . Haemolytic anaemia due to cold agglutinins was diagnosed, and erythromycin therapy for a suspected Mycoplasma pneumoniae infection was instituted . Serological testing revealed, however, that the infection was attributable to Chlamydia psittaci . The literature on psittacosis and haematological complications is reviewed . Cold agglutinins are sometimes found in association with psittacosis, but a concomitant haemolytic anaemia is rare.

J R Army Med Corps, 1989 Jun, 135(2), 88 - 90
Probable late congenital syphilis presenting as Clutton joints; Kabuubi JB; A patient who presented with recurrent bilateral knee effusions was found to have positive serum syphilis serology . She was treated with oral erythromycin to a total of 40 grams and intra-articular injection of steroids in the right knee joint . Late congenital syphilitic arthritis is discussed with a review of the literature.

Br J Clin Pharmacol, 1989 Jun, 27(6), 789 - 94
Lack of effect of spiramycin on cyclosporin pharmacokinetics; Vernillet L et al.; 1 . The influence of spiramycin coadministration on cyclosporin pharmacokinetics was studied in five renal transplant patients . The plasma concentrations of cyclosporin were measured both by non-specific radioimmunoassay (RIA) and high-performance liquid chromatography (h.p.l.c.) . 2 . The kinetics of cyclosporin were followed before treatment, and after 1 day and then 2 weeks of oral treatment with spiramycin (3 X 10(6) iu, twice daily) . The main pharmacokinetic parameters (the area under the plasma drug concentration-time curve, the maximum plasma drug concentration and the time to reach it) obtained both by RIA and h.p.l.c . were not modified by spiramycin cotreatment after 1 day, nor after 2 weeks of spiramycin administration . Therefore, the pharmacokinetics of cyclosporin (parent drug and parent drug plus metabolites) are not influenced by the coadministration of spiramycin macrolide at therapeutic dosage . 3 . Spiramycin may be preferable to other macrolide antibiotics known to interact with cyclosporin such as erythromycin or josamycin.

Minerva Pediatr, 1989 Jun, 41(6), 323 - 8
{Macrolide-theophylline interaction . Experiences in pediatrics}; Pavesio D et al.; Subjects suffering from bronchial asthma being treated with theophylline often have to be treated with an antibiotic during acute stages . The purpose of the present study is to assess to clearance variation in theophylline when a macrolide antibiotic is associated after theophyllinemia steady-state has been attained . It has been seen that macrolides interfere differently on the blood levels of theophylline . Whereas erythromycin and josamycin determine a significant reduction in theophylline clearance, Miocamycin seems not to modify this parameter significantly.

Antimicrob Agents Chemother, 1989 Jun, 33(6), 960 - 2
In vitro susceptibilities of Entamoeba histolytica to azithromycin, CP-63,956, erythromycin, and metronidazole; Ravdin JI et al.; Current therapy of Entamoeba histolytica infection requires use of multiple agents effective at different body sites, including the intestinal lumen, intestinal tissue, and liver . Azithromycin and CP-63,956, new extended-half-life macrolides which reach high levels in tissue, exhibit in vitro antiamebic activity at 18 or 48 h of incubation at concentrations comparable to that of erythromycin and slightly higher than that of metronidazole . Azithromycin and CP-63,956 have the potential to be useful therapeutic agents for all types of E . histolytica infection.

J Pediatr, 1989 Jun, 114(6), 934 - 9
Outbreak of pertussis in a residential facility for handicapped people; Fisher MC et al.; An outbreak of pertussis was recognized and investigated in a home for neurologically impaired people . Of 66 residents, 44 (67%) had evidence of recent pertussis infection, although only 12 (27%) had respiratory symptoms . Pertussis was diagnosed by culture, direct fluorescent antibody testing of nasal secretions, agglutinating antibody titer, pertussis antitoxin titer, IgG antibody to pertussis toxin, IgA antibody to pertussis toxin, IgA antibody to filamentous hemagglutinin, or IgG antibody to filamentous hemagglutinin . No single test identified more than 66% of people with pertussis . Of those with positive serologic findings, 95% had a positive test result for IgA antibody to filamentous hemagglutinin or for IgG antibody to pertussis toxin or for both . Pertussis occurred in both immunized and unimmunized residents . Seven carriers were identified; these residents had positive cultures or positive direct fluorescent antigen test results but negative serologic findings . Treatment of residents and caretakers with erythromycin halted the outbreak.

Diagn Microbiol Infect Dis, 1989 May-Jun, 12(3 Suppl), 89S - 91S
In vitro activity of lomefloxacin (SC 47111 or NY-198) against isolates of Legionella spp; Dubois J et al.; The in vitro activity of lomefloxacin (SC-47111 or NY-198) was compared with those of erythromycin and rifampin against a total of 180 Legionella spp . strains isolated from nosocomial or acquired respiratory tract infections and from environmental sources . Rifampin was the most active agent tested (MIC90, 0.008 microgram/ml) against Legionella spp . However, lomefloxacin was found 2-to-4-fold more active than erythromycin against most Legionella strains tested . Against Legionella pneumophila, lomefloxacin (MIC90, 0.12 microgram/ml) was significantly more than erythromycin (MIC90, 0.5 micrograms/ml) . L . pneumophila serogroup 2, 3, and 5 strains (MIC90, 0.06 micrograms/ml) were more susceptible than L . pneumophila serogroup 1, 4, 6, 7, and 8 (MIC90, 0.12 microgram/ml) . L . dumoffii was the most resistant species with a MIC90 of 0.25 microgram/ml and 0.5 microgram/ml, respectively, to lomefloxacin and erythromycin . The activity of lomefloxacin was similar against the isolates obtained from patients or from environmental sources.

J Emerg Med, 1989 May-Jun, 7(3), 249 - 51
Theophylline toxicity due to drug interaction; Tenenbein M; Acute theophylline toxicity is usually due to overdose . However, it may also be brought about by interference of its metabolism secondary to the concurrent administration of other drugs . Erythromycin is important in this regard as illustrated in the following case of a 16-year-old girl who developed theophylline toxicity while on therapy with both of these drugs . As well as the potential for theophylline toxicity, coadministration of these two drugs may result in subtherapeutic serum erythromycin concentrations . Thus, if at all possible, this practice should be avoided . If unavoidable, then serial serum theophylline concentrations should be monitored . The occurrence of this interaction is unpredictable . Thus the previous recommendation of decreasing the theophylline dosage by 25% to prevent toxicity during erythromycin therapy is irrational and should be avoided . Drug interactions should be considered in the differential diagnosis of theophylline toxicity.

Mol Pharmacol, 1989 May, 35(5), 626 - 34
Effects of a series of 4-alkyl analogues of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine on the major inducible cytochrome P-450 isozymes of rat liver; Riddick DS et al.; Various 4-alkyl analogues of 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) cause mechanism-based inactivation of cytochrome P-450 (P-450) by destroying the heme prosthetic group . We have examined the isozyme selectivity of representative DDC analogues with respect to the major inducible P-450 isozymes of rat liver . Hepatic microsomes from untreated, phenobarbital (PB)-treated, beta-naphthoflavone (beta NF)-treated, and dexamethasone (DEX)-treated rats were incubated with a DDC analogue and NADPH and were subsequently analyzed for P-450 and heme content, P-450 isozyme immunoreactivity, and enzyme activity . Compared with the uninduced state, 4-isopropyl-DDC caused slightly less P-450 destruction following beta NF induction and much greater destruction following DEX pretreatment . Also, 4-hexyl-DDC was found to cause less P-450 destruction following PB or DEX pretreatment, compared with results obtained with untreated rats . These results suggest that DDC analogues possess different isozyme selectivity profiles . Monoclonal antibodies (MAbs) directed against the major inducible isozymes of P-450 were used to probe Western blots of microsomal protein following DDC analogue treatment . The formation of lower molecular mass (45-55 kDa) immunoreactive proteins in microsomes from beta NF-treated rats following DDC analogue treatment was revealed by two MAbs (1-31-2 and 1-36-1), suggesting that the apoprotein of the major beta NF-inducible isozyme, P-450c, is subject to alteration by DDC analogues . In microsomes from DEX-treated rats, DDC analogues caused the formation of higher molecular mass (80, 94, and 115 kDa) proteins showing immunoreactivity with MAb 2-13-1, directed against a major DEX-inducible isozyme belonging to the P-450p family . These immunochemical findings are supported by the demonstration that DDC analogues also caused mechanism-based inhibition of the catalytic activity of P-450c (7-ethoxyresorufin O-deethylase) and P-450p (erythromycin N-demethylase) but not that of the major PB-inducible isozyme, P-450b (7-pentoxyresorufin O-dealkylase) . The combined immunochemical and enzymic studies indicate that rat liver P-450 c and p are targets for mechanism-based inactivation by DDC analogues.

Mol Pharmacol, 1989 May, 35(5), 610 - 6
Evidence for a PCN-P450 enzyme in chickens and comparison of its development with that of other phenobarbital-inducible forms; Lorr NA et al.; Of four monoclonal antibodies to purified rat liver cytochrome P450s, including those from 3-methylcholanthrene-, phenobarbital-, ethanol-, and pregnenolone-16-alpha-carbonitrile-treated rats, only the monoclonal antibody against pregnenolone-16-alpha-carbonitrile-inducible P450 immunodetected proteins in chicken liver microsomes after blotting from sodium dodecyl sulfate-polyacrylamide gels . This protein migrated identically with the pregnenolone-16-alpha-carbonitrile-inducible P450 detected in microsomes from dexamethasone-treated rats . It was most predominant in liver microsomes from chickens at 1 day posthatching, whereas much lower levels were observed in the embryo and at 36 days posthatch . Phenobarbital and dexamethasone were both effective inducers of this protein . The developmental profile and induction by phenobarbital and dexamethasone of several cytochrome P450-associated catalytic activities were compared with those of the immunodetected protein . Chicken liver microsomal erythromycin demethylase, a characteristic activity of rat pregnenolone-16-alpha-carbonitrile-inducible P450, was similar in developmental profile and induction to the immunodetected protein, with a high degree of augmentation at 1 day posthatch compared with that in the embryo and at 36 days posthatch; aldrin epoxidase, benzphetamine demethylase, ethylmorphine demethylase, and aminopyrine demethylase were more similar to each other in development and induction and were less well correlated with the immunodetected protein . This evidence suggests the presence in chicken liver of at least two types of P450, one a form related to the pregnenolone-16-alpha-carbonitrile-inducible P450 family . All of the catalytic activities were induced after pretreatment of chickens with phenobarbital but aldrin epoxidase was most effectively induced . Aldrin epoxidase was also detected in microsomes from untreated embryos as early as 7 days of incubation . Erythromycin demethylase was the only catalytic activity induced by dexamethasone . There was a trend of increased specific activity toward all the substances after hatching, indicating a more efficient P450 system, possibly due to a sharp increase in some isozymes, including the form from the pregnenolone-16-alpha-carbonitrile-inducible P450 family . This evidence for a pregnenolone-16-alpha-carbonitrile-inducible P450 in chickens agrees with sequence information that suggests the early evolution of this form and demonstrates the suitability of the chicken for studies of P450 evolution.

J Int Med Res, 1989 May-Jun, 17(3), 287 - 94
Comparison of two oral forms of erythromycin in the treatment of acute respiratory tract infections . A multicentre general practice study; Macklin J et al.; A total of 1244 patients with acute upper or lower respiratory tract infection were randomized to receive, twice daily for 7 days, either capsules of enteric-coated pellets of erythromycin base at a dose of 1 g/day or erythromycin ethylsuccinate tablets at a dose of 2 g/day in a single-blind, multicentre study . The efficacy of each formulation was similar, with about 90% of patients who had completed at least 5 days of treatment being reported as either cured or improved . Gastro-intestinal symptoms were the most commonly reported side-effects, being significantly more frequent in patients receiving erythromycin base . Gastro-intestinal intolerance was also the main reason for discontinuing either treatment, although it was a significantly more frequent reason in patients given erythromycin base . This study indicates that both formulations of erythromycin are highly effective for routine, empirical treatment of acute respiratory tract infections . Erythromycin base, however, appears to be less well tolerated than erythromycin ethylsuccinate.

Indian Pediatr, 1989 May, 26(5), 435 - 9
Study of diphtheria carriers in Miraj; Udgaonkar US et al.; Following a case of diphtheria, 131 contacts were studied for throat and nose carriage . The carriage of C . diphtheriae was found to be 19.8%, 65.3% of them were toxin producing by counter-immunoelectrophoresis (CIEP) . The carriers were treated with erythromycin for 7 days . Repeat swabs found them to be negative for C . diphtheriae except in four who had erythromycin resistant and penicillin sensitive strains . Penicillin treatment eliminated the organisms.

Med Clin (Barc), 1989 Apr 29, 92(16), 605 - 7
{Pleural empyema caused by Legionella pneumophila}; Ribera E et al.; Although pleural effusion is not uncommon in legionellosis, the development of empyema and the demonstration of the organism in pleural fluid are exceptional . We report four patients with pleural empyema with isolation of Legionella pneumophila in the pleural fluid culture . The patients were three males and one female, with ages ranging from 36 and 83 years . All had left pleuritic pain, fever and pleural effusion . The appearance of pleural effusion was purulent in two cases and serofibrinous in the other two . Initially, the diagnosis was only suspected in one patient . The other three received inadequate treatment, until the result of the culture of the pleural fluid in BCYE-alpha medium was known . After giving erythromycin therapy at high doses, the outcome was favorable in the four patients . It is concluded that, in the absence of another diagnosis, the presence of L . pneumophila should be systematically investigated in the pleural fluid although the disease is not clinically suspected.

J Antimicrob Chemother, 1989 Apr, 23 Suppl D, 71 - 7
Single-dose cefmetazole versus multiple dose cefoxitin for prophylaxis in abdominal surgery; DiPiro JT et al.; One hundred and ninety-five patients undergoing abdominal surgical procedures completed a multicentre, randomized, open-label study comparing the safety and efficacy of cefmetazole and cefoxitin for the prevention of postoperative wound infection . Cefmetazole was administered iv in a single 2 g dose given within 90 min of the operation . Cefoxitin was administered in a single 2 g, similarly timed, preoperative dose and two additional doses given at 6 h intervals after surgery . For operations that exceeded 2-4 h duration an additional dose of each agent was administered . Patients undergoing colorectal operations received oral neomycin and erythromycin as bowel preparation . Colorectal operations were performed most frequently (49% of patients) followed by cholecystectomies (26%) and gastroduodenal procedures (21%) . The operative site infection rate was 6.5% for cefmetazole and 7.7% for cefoxitin (P greater than 0.05) . Serious drug related adverse effects were not observed . This study demonstrates that administration of single-dose cefmetazole is as effective as a standard three dose regimen of cefoxitin for prophylaxis with abdominal operations.

Am J Dermatopathol, 1989 Apr, 11(2), 177 - 81
AIDS-related angiomatosis; Axiotis CA et al.; We report multifocal cutaneous and mucosal vascular proliferations with the clinical and histological features of lobular capillary hemangioma and histiocytoid hemangioma in a 32-year-old acquired immunodeficiency syndrome patient . The lesions resolved subsequent to erythromycin therapy.

Br J Clin Pharmacol, 1989 Apr, 27(4), 475 - 81
Cyclosporin-erythromycin interaction in renal transplant patients; Gupta SK et al.; 1 . The interaction between cyclosporin (CyA) and erythromycin was studied in renal transplant patients following oral and intravenous administration of CyA . 2 . Blood and plasma CyA concentrations and blood concentrations of metabolite 17 were measured by h.p.l.c . 3 . Erythromycin produced almost a two-fold increase in bioavailability, from 36% to 60%; with a small (13%) decrease in clearance of CyA . 4 . The metabolite 17 data further support the postulate that erythromycin increases the absorption of CyA rather than inhibits its metabolism, as generally believed.

Postgrad Med, 1989 Apr, 85(5), 303 - 8, 313-4
Lyme disease . The hidden pandemic; Hamilton DR; Physicians will recognize Lyme disease faster if they maintain a high index of suspicion in a young patient with arthritis accompanied by negative rheumatoid factor and antinuclear antibody in combination with cardiac conduction problems or lymphocytic meningitis . The Lyme spirochete (Borrelia burgdorferi) has notable sensitivity to tetracycline, penicillin, and erythromycin; therefore, proper and complete treatment of the disease, once it is identified, can be easily achieved . Finkel observed that Lyme disease manifests itself as a "great imitator," as do many disorders caused by a spirochete . The total impact of Lyme disease on public health will be known only when the disease is fully recognized, consistently reported, and adequately managed.

N Engl J Med, 1989 Mar 23, 320(12), 769 - 72
Efficacy of neonatal ocular prophylaxis for the prevention of chlamydial and gonococcal conjunctivitis; Hammerschlag MR et al.; Opinions differ concerning the efficacy of prophylaxis against neonatal chlamydial and gonococcal conjunctivitis . From January 1986 through June 1988, we gave all infants born at Kings County Hospital Medical Center one of three prophylactic agents -- silver nitrate drops, erythromycin ophthalmic ointment, or tetracycline ophthalmic ointment . The treatments were rotated monthly . Gonococcal ophthalmia occurred in 8 of the 12,431 infants born during the study (0.06 percent), 1 in the silver nitrate group, 4 in the erythromycin group, and 3 in the tetracycline group (P not significant) . Seven of these infants were born to women who had received no prenatal care . From September 1985 through December 1987, we screened 4357 pregnant women for cervical chlamydial infection, of whom 341 (8 percent) had positive cultures . Of their offspring, 230 were evaluated for neonatal chlamydial conjunctivitis; the incidence was 20 percent in the silver nitrate group, 14 percent in the erythromycin group, and 11 percent in the tetracycline group (P not significant) . We conclude that neonatal ocular prophylaxis with either erythromycin or tetracycline ophthalmic ointment does not significantly reduce the incidence of chlamydial conjunctivitis in the offspring of mothers with chlamydial infection as compared with silver nitrate, and that better management of maternal chlamydial infection is therefore required . We also conclude that there is a small but appreciable incidence of neonatal gonococcal ophthalmia that could be prevented by better prenatal screening and treatment of maternal gonococcal infection.

J Mol Biol, 1989 Mar 5, 206(1), 69 - 79
ermC leader peptide . Amino acid sequence critical for induction by translational attenuation; Mayford M et al.; The ermC mRNA leader segment, which encodes a 19 amino acid leader peptide, MGIFSIFVISTVHYQPNKK, plays a key role in regulating expression of the ErmC methylase . The contribution of specific leader peptide amino acid residues to induction of ermC was studied using a model system in which the ErmC methylase was translationally fused to Escherichia coli beta-galactosidase as indicator gene . Codons of the ermC leader peptide were altered systematically by replacement of leader DNA segments with double-stranded DNA constructed from chemically synthesized oligonucleotides . Missense mutations that resulted in reduced efficiency of induction involved codons for amino acid residues 5 to 9 (-SIFVI-) . Nonsense mutations causing termination of the leader peptide at codons 10 (-S-) or 12 (-V-) remained inducible . These findings suggest that the codons for residues 5 to 9 of the leader peptide comprise the critical region in which ribosomes stall in the presence of erythromycin.

Eur Respir J, 1989 Mar, 2(3), 263 - 6
Q fever pneumonia: a review of 164 community-acquired cases in the Basque country; Sobradillo V et al.; One hundred and sixty four cases of Q fever pneumonia are reviewed . Coxiella burnetti is responsible for 18.8% of pneumonias acquired in the community in our region with an extremely high seasonal variation . 91% of the cases occur between January and June . 88.5% of the patients are less than 40 yrs of age and 77% are male . The most common clinical symptoms are high fever, cough, cephalalgia and myalgias . 46.5% of the patients have no respiratory symptoms although 34% of the cases report pleural pain . The radiological signs are nonspecific . With regard to laboratory data, it is often observed that the white blood cell count (WBC) is normal and the liver enzymes are abnormal (45%) . Treatment with doxycycline reduces the fever more quickly than erythromycin.

Eur Respir J, 1989 Mar, 2(3), 257 - 62
Incidence and clinical features of community-acquired legionellosis in hospitalized patients; Ruf B et al.; In a two-year prospective study of patients hospitalized because of community-acquired pneumonia, the incidence of legionellosis was found to be 3.8% (17/442 cases) . After S . pneumoniae, M . pneumoniae and influenzae viruses, legionellae were the fourth most frequently identified pneumonia agents . We evaluated the clinical data from 41 cases with legionellosis, 17 diagnosed in this prospective study and 24 prior to the study . The age range of all patients (22 women, 19 men) was 24-78 yrs (median 61.3 yrs), 14 of 41 cases (34.1%) had extrapulmonary organ involvement . Twelve patients (29.3%) died . The fatality rate was 4.5% (1/22 cases) in patients treated with erythromycin, and 57.9% (11/19 cases) in patients treated with other antibiotics . Antibiotics effective in legionellosis should be added to the routine therapy of community-acquired pneumonia when this aetiology can not be excluded.

Semin Respir Infect, 1989 Mar, 4(1), 4 - 11
Pneumococcal pneumonia; Coonrod JD; Pneumococci remain the most common cause of community-acquired pneumonia, and there are still important questions concerning the pathogenesis, management, and prevention of this disease . Infection begins by aspiration of pneumococci from the oropharynx . Alveolar macrophages, granulocytes, and extra-cellular factors, including opsonins, are necessary for control of bacterial proliferation and cure of the infection . Clinically, pneumococcal pneumonia often presents with sudden onset of productive cough, fever, and a rigor, but symptoms may be muted in the young, elderly, or debilitated . About one-fourth of patients have a positive blood culture . Examination of sputum by Gram's stain and culture can provide useful information, but are not definitive . Tests for soluble pneumococcal antigen or the direct quellung reaction on sputum have not proved helpful . Pneumococci isolated from blood and spinal fluid should be tested for penicillin sensitivity routinely . Penicillin G and erythromycin are the mainstays of specific treatment, and rapid subjective improvement on narrow-spectrum therapy is an important point in diagnosis . The mortality rate continues to be about 18%, and prevention by vaccination remains a highly desirable goal.

Postgrad Med, 1989 Mar, 85(4), 109 - 13
Chlamydial infections . Gaining control of a growing epidemic; Setness PA; Infections caused by Chlamydia trachomatis are wide-spread, costly, and damaging . Consequences are harshest for women because of the adverse effects on the reproductive system . Newborns of infected mothers may also be affected . Screening of sexually active patients is important, because many infected patients are asymptomatic . Newer, improved laboratory techniques are available . Treatment with doxycycline, tetracycline, or erythromycin is preferred . Simultaneous treatment of sexual partners is vital.

Drug Metab Dispos, 1989 Mar-Apr, 17(2), 197 - 207
Metabolism of cyclosporin A . IV . Purification and identification of the rifampicin-inducible human liver cytochrome P-450 (cyclosporin A oxidase) as a product of P450IIIA gene subfamily; Combalbert J et al.; A cytochrome P-450 involved in the metabolism of cyclosporin A (CsA) was isolated and purified to electrophoretic homogeneity from human liver microsomes of renal transplant donors . This cytochrome, designated P-450(CsA), exhibited a type I binding spectrum in the presence of CsA with a Ks(app) of 25 microM, a molecular weight of 52 kDa on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and a maximal absorbance at 449 nm when reduced in the presence of carbon monoxide . The N-terminal sequence of P-450(CsA), determined by Edman degradation reaction, was 63% homologous with that of the rabbit liver CsA oxidase P-450 3c and 100% homologous with that of the human liver isozyme P-450(HLp/NF), recently identified as the human nifedipine (NF) oxidase . Polyclonal and monoclonal antibodies directed against P-450 3c and P-450(HLp/NF), respectively, recognized native microsomal and highly purified P450(CsA) . As observed in the rabbit, human liver microsomes were shown to generate mono- and dihydroxy, as well as dihydroxy and/or monohydroxy N-demethylated, derivatives of CsA . Production of these metabolites was shown to be specifically inhibited by anti-P-450 3c polyclonal antibodies . CsA oxidase, NF oxidase, and erythromycin demethylase were shown to be closely correlated with the level of P-450(CsA) determined from Western blot or enzyme-linked immunosorbent assay . Moreover, these monoxygenase activities and the hepatic level of P-450(CsA) were simultaneously increased in the liver of patients treated for 4 days with 600 mg of rifampicin per day . Finally, NF was shown to be a competitive inhibitor of CsA oxidation and vice versa . We conclude that P-450(CsA) is responsible for most (80%) of CsA oxidase activity in human liver, is encoded by gene P450IIIA3, as is NF oxidase, or a very closely related gene, and is strongly inducible by rifampicin pretreatment.

Semin Respir Infect, 1989 Mar, 4(1), 19 - 31
Pneumonia caused by Mycoplasma pneumoniae and the TWAR agent; Atmar RL et al.; Mycoplasma pneumoniae and the TWAR agent account for a good proportion of pneumonias acquired in the community among older children and young adults . Recovery from these infections is common, although serious complications may occur . Each is associated with fever, nonproductive cough, and headache . The full clinical manifestations of TWAR agent infection are only now beginning to be defined . Diagnosis of M pneumoniae can be by serology and/or culture capabilities . The TWAR agent cannot be routinely isolated and serologic tests are available only in research laboratories . Response to tetracycline antibiotics has been established for each agent and hospitalization is rarely needed . Erythromycin and other macrolide antibiotics have good activity against M pneumoniae and can be employed as an alternative to tetracycline antibiotics for this pathogen.

Postgrad Med, 1989 Mar, 85(4), 379 - 86
Branhamella infections . An increasingly common respiratory illness; Feleke G et al.; Branhamella catarrhalis is an important cause of acute sinusitis and otitis media in children and of acute tracheobronchitis in older persons with underlying chronic lung disease or a suppressed immune system . Clinical presentation of B catarrhalis infection varies from a mild, self-limiting disease to severe pneumonia, but most cases are mild to moderate in severity . Infection occurs sporadically, and endogenous spread from the oropharynx is the likely mechanism . The keys to diagnosis are a high index of clinical suspicion, correct interpretation of Gram's stain of sputum, and subsequent confirmation on culture . Because most strains of B catarrhalis produce beta lactamase, antibiotics that resist beta-lactamase production, eg, amoxicillin-clavulanic acid (Augmentin), erythromycin, ciprofloxacin (Cipro), are recommended . Mild infections can be self-limiting and may not require antibiotic therapy.

J Gen Microbiol, 1989 Mar, 135 ( Pt 3), 575 - 81
Some properties of two erythromycin-dependent strains of Escherichia coli; Maguire BA et al.; Strains of Escherichia coli can be isolated that require erythromycin for growth . With one strain, AM, a range of antibiotics, including chloramphenicol, tetracycline, spectinomycin, kasugamycin and rifampicin, will substitute for erythromycin on solid and in liquid media; nalidixic acid supports growth in liquid but not on solid media . With a second strain, 103, chloramphenicol, tetracycline and spectinomycin support growth in liquid media but on solid medium only chloramphenicol substitutes for erythromycin . In media of higher than normal ionic strength, strain AM, but not strain 103, can grow in the absence of antibiotics . Possible reasons for these complex phenotypes are discussed.

Z Hautkr, 1989 Feb 15, 64(2), 129 - 31
{Significance of the dose of josamycin in the treatment of chlamydia infected pregnant patients}; Soltz-Szots J et al.; Erythromycin and josamycin are the antibiotics of choice in the treatment of pregnant women with Chlamydia infection . On the basis of differing recommendations in the literature regarding treatment period and dosage, two groups of pregnant women were treated with josamycin according to different dosage schedules: Group A: 170 patients treated with 2 x 500 mg daily for 12 days . Group B: 120 patients treated with 3 x 500 mg daily for 8 days . The diagnosis was confirmed by immunofluorescence with monoclonal antibodies . Non-responding patients were treated again with a similar dose . 17% of the patients in group A and 9.1% in group B were still positive for Chlamydia after the first course of treatment . After a second course, 13.6% of group A and none of group B showed positive controls . Failures of therapy after the first treatment course can be attributed to errors in dosage or re-infection, whereas failures after the second course must be due to bad compliance . Our results suggest that pregnant women with Chlamydia infection are most efficiently treated with high dosages of josamycin over a short period of time.

J Clin Invest, 1989 Feb, 83(2), 688 - 97
Erythromycin breath test as an assay of glucocorticoid-inducible liver cytochromes P-450 . Studies in rats and patients; Watkins PB et al.; The major P-450IIIA gene family member present in human liver is HLp which, like its rat liver orthologue P-450p, is inducible by glucocorticoids and catalyzes erythromycin N-demethylation . To develop a practical method to estimate the amounts of HLp in patients {14C}N-methyl erythromycin was injected into rats that had been pretreated with dexamethasone or with inducers of other forms of cytochrome P-450 . The rate of demethylation of this substrate, measured simply as 14CO2 in the breath, correlated well with the concentrations of immunoreactive P-450p protein (r = 0.70), holocytochrome P-450p (r = 0.70), or with erythromycin N-demethylase activity (r = 0.90) determined in the liver microsomes prepared from each rat . Next, {14C}N-methyl erythromycin was administered to 30 patients and there was a sixfold interindividual variation in breath 14CO2 production seemingly unrelated to medications, smoking status or age . However, the average breath test values were twofold greater in female as compared to male patients (P less than 0.01) . Breath 14CO2 production rose in patients retested after treatment with the P-450IIIA inducers dexamethasone (P less than 0.05) or rifampicin (P less than 0.05) and was decreased after treatment with the HLp inhibitor triacetyloleandomycin (P less than 0.05) . We conclude that the erythromycin breath test provides a convenient assay of P-450IIIA cytochromes in rats and in some patients.

Am J Surg, 1989 Feb, 157(2), 264 - 71
Cyclosporine pharmacokinetic drug interactions; Baciewicz AM et al.; Cyclosporine (CyA) is commonly prescribed as an immunosuppressive to prevent rejection of organ transplants . Numerous pharmacokinetic drug interactions of potential clinical significance exist because other drugs may induce or inhibit the metabolism of CyA . Case reports and studies demonstrate that rifampin, phenytoin, phenobarbital, and carbamazepine may induce the hepatic metabolism of CyA, causing decreased CyA concentrations . Graft rejection through inadequate immunosuppression may be associated with subtherapeutic or decreased CyA levels . Erythromycin, ketoconazole, calcium channel blockers, and sex hormones appear to inhibit CyA metabolism, causing increased CyA concentrations . Signs and symptoms of renal, hepatic, or neurotoxicity may be evident with increased or toxic CyA levels . Mutual inhibition of metabolism occurs between CyA and corticosteroids . Intravenous sulphadimidine and trimethoprim may cause decreased CyA concentrations by an unknown mechanism.

J Am Osteopath Assoc, 1989 Feb, 89(2), 195 - 7
Bronchial and gastrointestinal cryptosporidiosis in AIDS; Goodstein RS et al.; Cryptosporidiosis is a coccidial protozoan initially reported in domestic animals . It is primarily a gastrointestinal organism that does not invade mucosa . It was first described in 1976 in developing countries as an etiology of infantile diarrhea with inanition and malnutrition . Gastrointestinal involvement in patients with AIDS has been increasingly reported . We report a case of combined gastrointestinal and bronchial cryptosporidiosis . Cryptosporidium is an acid-fast organism which was successfully treated with erythromycin.

Genitourin Med, 1989 Jan, 65(1), 32 - 4
Bacampicillin to treat non-gonococcal urethritis in men: pilot study; Lee CT et al.; Of 84 men with non-gonococcal urethritis (NGU), 24 yielded Chlamydia trachomatis by either cell culture or MicroTrak immunofluorescence test . All 84 were treated with bacampicillin 800 mg twice a day for seven days . Five (one chlamydia positive) defaulted from follow up 10 to 14 days after the start of treatment . Of the 23 chlamydia positive patients who attended follow up, 22 became chlamydia negative; 14 of the 23 patients also became asymptomatic and had normal urethral smears . Of the 56 chlamydia negative patients who attended follow up, 21 were cleared of their urethritis . Two patients reported side effects; one drowsiness and one mild diffuse alopecia . Bacampicillin may therefore be a safe and effective alternative to tetracycline or erythromycin in treating chlamydial urethritis in men.

Toxicol Lett, 1989 Jan, 45(1), 101 - 10
Validation of a morphometric analysis procedure using indomethacin-induced alterations in cultured hepatocytes; Sorensen EM; Morphometric analysis was used to quantitate indomethacin-induced morphological changes in primary cultures of neonatal rat hepatocytes by comparison with standard assessments of functional integrity (i.e . enzyme release, urea levels, and dye exclusion) . For this procedural validation, indomethacin concentrations were selected to correspond to the therapeutic plasma levels of rheumatoid arthritic or systemic lupus erythematosus patients having liver cell injury secondary to prolonged, high-dose administration of this nonsteroidal antiinflammatory agent . Primary cultures of neonatal rat hepatocytes were exposed for 12 h to 0, 100, 500 or 1000 microM indomethacin and subjected to a double-blind morphometric analysis procedure modified for use on cultured cells . This procedure systematically converted two-dimensional morphologic information into three-dimensional numerical data for statistical analysis . These optical measurements provided an accurate analysis following 4 h of measurements . When the concentration of indomethacin was increased from 0 to 1000 microM, the relative volume percent of Type I cells decreased . Therefore these cells, which were indistinguishable from healthy, untreated control cells, become less numerous as toxicant level increased . In contrast, the relative volume percent values of other progressively more damaged cell types (i.e . Types II, III, and IV cells) increased with elevation of indomethacin levels . Morphometric assessments paralleled functional assessments of indomethacin-induced cytotoxicity (r2: 0.88-0.99) . Therefore, the present study validated this morphometric analysis procedure using a rigorous cellular exposure which caused substantial cell injury and subsequent lifting of 23% cells from the substrate . Combined with previous validation studies involving cadmium, erythromycin and benoxaprofen, the present study showed that morphometric analysis is a rapid, accurate method for the measurement of cell injury in cultured parenchymal hepatocytes.

Ther Drug Monit, 1989, 11(1), 47 - 52
Erythromycin effects on multiple-dose carbamazepine kinetics; Miles MV et al.; To determine the effects of erythromycin on multiple-dose carbamazepine pharmacokinetics, seven healthy male volunteers were given 300-400 mg of carbamazepine each morning for 17 consecutive days . All subjects were given a placebo erythromycin form every 6 h on days 12, 13, and 14, then changed to erythromycin base 250 mg every 6 h for the final 3 days . Serial blood samples were drawn after the morning doses on days 14 and 17 . Analysis of carbamazepine and carbamazepine-10,11-epoxide concentrations were made by high-performance liquid chromatography . Pharmacokinetic analysis showed carbamazepine half-life and 24-h postdose concentration to increase significantly (p less than 0.05) and oral clearance to decrease (p less than 0.05) during erythromycin administration . Decreases in carbamazepine-10,11-epoxide Cmax (p less than 0.001), area under the concentration-time curve0-24 (p less than 0.001), and carbamazepine-10,11-epoxide to carbamazepine ratio (p less than 0.01) also occurred during carbamazepine dosing . Erythromycin significantly inhibits the epoxide-diol metabolic pathway by which carbamazepine is transformed to carbamazepine-10,11-epoxide . Wide individual variability in this interaction should serve to warn practitioners of the unpredictability of this interaction.

Dis Colon Rectum, 1989 Jan, 32(1), 17 - 20
Metronidazole vs . erythromycin, neomycin, and cefazolin in prophylaxis for colonic surgery; Khubchandani IT et al.; A prospective, double-blind, randomized study was undertaken to compare perioperative parenteral metronidazole and erythromycin, One neomycin, and cefazolinhundred fifty-five patients were randomized into two groups by the pharmacy department . The resulting difference between the overall septic complication rate in patients receiving erythromycin, neomycin, and cefazolin (10.9 percent) and the rate in patients receiving metronidazole alone (31.9 percent) was significant . This indicates that an antibiotic to cover aerobic bacteria should be added to the regimen when metronidazole is used.

Arch Dermatol, 1989 Jan, 125(1), 82 - 4
Failure of erythromycin to cure secondary syphilis in a patient infected with the human immunodeficiency virus; Duncan WC; The case presented here involves a 32-year-old homosexual man with human immunodeficiency virus seropositivity and secondary syphilis . Because of possible penicillin allergy, he was initially treated with erythromycin base by mouth . During four weeks of therapy, his cutaneous lesions worsened as did his systemic symptoms . Following desensitization and parenteral penicillin therapy, his cutaneous lesions and symptoms rapidly resolved . His VDRL titer fell appropriately.

Vestn Dermatol Venerol, 1989, (8), 7 - 9
{Disordered calcium metabolism in Reiter's disease}; Mavrov II et al.; Cellular (erythrocytic) and extracellular (blood serum) calcium levels have been measured in patients with Reiter's disease and with urogenital chlamydiosis over the course of treatment . Calcium metabolism disorders depending on the disease severity have been detected in chlamydiosis patients . Calcium homeostasis imbalance manifests as a significant rise of the red cell calcium level in the presence of normal Ca ion concentration in the blood serum, which fact may result from impaired Ca ion transport through the plasma membrane . Combined therapy, including erythromycin, resulted, besides Chlamydia elimination, in normalization of Ca metabolism parameters under study.

Microbios, 1989, 57(232-233), 167 - 78
Comparative effects of roxithromycin and erythromycin on cellular immune functions in vitro . 1 . Uptake of 3H-macrolides by human macrophages; Cuffini AM et al.; The degree of penetration of roxithromycin in human macrophages was evaluated and compared with that of erythromycin . The results indicated that both macrolides at concentrations of 2, 10 and 20 micrograms/ml were concentrated by macrophages, even if roxithromycin was consistently and significantly more accumulated than erythromycin . Comparison of the degree of penetration of the two drugs into dead, resident and stimulated phagocytes indicated that the process of transfer through the macrophage wall was of an active nature, related to the metabolic state of the cells . Analysis of the binding of the two macrolides to intracellular proteins showed that more binding sites were available for erythromycin than for roxithromycin.

J Clin Pharmacol, 1989 Jan, 29(1), 79 - 84
Effect of a high-fat meal on the bioavailability of a polymer-coated erythromycin particle tablet formulation; Randinitis EJ et al.; The effect of food on the relative bioavailability of an erythromycin particles-in-tablet formulation was studied in 27 healthy volunteers, using a four-way, crossover study design with the following treatments: one or two erythromycin capsules USP (Eryc, Parke-Davis), or one polymer-coated erythromycin particles-in-tablet (PCE, Abbott) administered fasting or with a high-fat meal . Under fasting conditions the erythromycin particles-in-tablet and erythromycin capsule formulations are bioequivalent based on similar tmax and dose-normalized Cmax and AUC values . The rate and extent of absorption from the particles-in-tablet formulation, however, are dramatically reduced following administration with a meal . Mean Cmax and AUC values decreased by 73% and 72%, respectively, and seven subjects had no detectable erythromycin plasma concentrations for 16 hours following administration of the particles-in-tablet formulation with the high-fat meal . Greater than 40% of the subjects had nonfasting Cmax and AUC values that were less than 10% of those values following administration of the dose fasting . Cmax and AUC values in nonfasting subjects were within 75% to 125% of fasting values in only two and one of 27 subjects, respectively . The erythromycin particles-in-tablet formulation therefore should not be administered with meals.

J R Nav Med Serv, 1989 Winter, 75(3), 143 - 6
Leptospirosis . Do you consider the diagnosis?
Rudland SV.
Patients with Leptospirosis, usually a water borne zoonotic disease, are likely to present themselves to Royal Naval primary health carers, who deal with a young active population, frequently participating in watersports . Leptospira, which belong to the order Spirochaetaceae, comprise of two distinct species . Within each species there are a number of serologically different serovars (serotypes), arranged in related serogroups . L . interrogans var Icterhaemorrhagiae and L . interrogans var Hebdomadis serovar hardjo are the most commonly reported organisms in Great Britain . Traditionally water and sewage workers have been amongst those most frequently infected, but with improved health care awareness this group has been overtaken by farmworkers, and a growing group of people engaged in aquatic sports . Symptoms of Leptospiral infection vary in severity from a mild flu-like illness to symptoms resulting from severe renal, hepatic or meningeal involvement . Mild symptoms respond to oral penicillin, erythromycin or tetracyclines, whilst more serious illness requires i.v . penicillin and supportive nursing . Spirochaetes can be detected in culture using darkground microscopy, and sero-conversion detected by IgM specific dot ELISA techniques . Suspected sera should be sent to PHLS Leptospira Reference Unit, County Hospital, Hereford . HR1 2ER . (Tel: 0432 277117).

Ann Med Interne (Paris), 1989, 140(7), 589 - 92
{Drug-induced pleural pathology (excluding antineoplastic chemotherapy)}; Haas C et al.; Drug-induced pleural side effects are rare and not usually identified . They may be a fibrous thickening of the pleura or an effusion, generally associated with an interstitial pneumopathy . Sometimes the pleural fluid is clear, sometimes hemorrhagic, and of varied cytological composition . The effusion can be uni- or bilateral . In the majority of cases, the pleural involvement stops when the causative agent is withdrawn . The pathology is usually attributed to a hypersensitivity mechanism when the following drugs have been given: nitrofurantoin, salazopyrine, erythromycin, ampicillin, gold salts, phenytoin, methysergide, ergotamine and bromocriptine . Some pleural lesions resemble lupus (induced by beta-blockers, hydralazine or procainamide) . Amiodarone can cause fibroses or effusions via a toxic or hypersensitivity mechanism . In some instances, the mechanism remains unknown (1 case with imipramine, 1 case of fibrosis with perhexiline, 1 case of effusion with ibuprofen, 4 cases of effusion induced by dandrolene).

Bull Soc Pathol Exot Filiales, 1989, 82(4), 575 - 7
{Q fever in Guinea-Bissau . 1 case}; Lyagoubi M et al.; Q fever is seldom reported in West Africa . The case of a man returning from Guinea Bissau who presented an acute lobar pneumonia with fever, headache, hematuria and hepatitis was confirmed by high titers of antibody in Phase II indirect immuno-fluorescence which appeared on the twelfth day of fever . Treatment with erythromycin was continued by doxycyclin, and complete resolution of all signs was promptly obtained . Coxiella Burnetii might thus be responsible of cases of unexplained fever with respiratory or hepatic manifestations in West Africa.

Sex Transm Dis, 1989 Jan-Mar, 16(1), 32 - 5
Treatment of nongonococcal urethritis: comparison of ofloxacin and erythromycin; Ibsen HH et al.; Ofloxacin, a new quinolone carboxylic acid derivative, has been reported to be effective and safe in the treatment of nongonococcal urethritis (NGU) . In the present investigation 188 male outpatients with NGU were randomized to double-blind treatment with either erythromycin (500 mg twice a day) or ofloxacin (200 mg twice a day) for seven days . Before therapy Chlamydia trachomatis was isolated from 43.6% of the patients . One relapse and one reinfection occurred in the erythromycin-treated group, whereas all patients in the group given ofloxacin were culture-negative at follow-up . Among the C . trachomatis-positive group of patients, the clinical efficacy of ofloxacin was 83.7%, and that of erythromycin, 77.4% at the final follow-up . In the C . trachomatis-negative group, the efficacy of ofloxacin was 93%, and that of erythromycin, 84.3% . The differences are not significant . No serious adverse effects were demonstrated . The results indicate that ofloxacin might be a valuable alternative for the treatment of NGU in men.

DICP, 1989 Jan, 23(1), 40 - 4
Intravenous erythromycin lactobionate-induced severe nausea and vomiting; Seifert CF et al.; Intravenous erythromycin lactobionate has been used for several years to treat various infectious diseases . Several cases of severe nausea and vomiting associated with its use have been reported in Europe but only a few cases have been reported in the U.S . The official product information does not refer to severe nausea and vomiting associated with its intravenous use; however, we report six additional cases of severe nausea and vomiting associated with rapid administration of erythromycin lactobionate, and review the current literature on the characteristics of this adverse effect.

Arch Immunol Ther Exp (Warsz), 1989, 37(3-4), 405 - 13
Effect of erythromycin treatment on specific immunologic response in mice; Nicolas R et al.; Six week old Swiss mice were sensitized by subcutaneous injection of 10(7) sheep red blood cells without adjuvant . One hour after sensitization, the mice were treated with erythromycin lactobionate for ten days . The minimal (15 mg/kg/day) and maximal (57 mg/kg/day) doses clinically used were assayed . The daily dose of erythromycin was administered intraperitoneally, in two injections, one every 12 hours . The kinetics of delayed type hypersensitivity reaction, measured by means of the foot-pad test, was evaluated by challenging different groups of fourteen mice with an eliciting dose of 10(8) SRBC injected into the foot-pad on days 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 after sensitization . Total and 2-mercaptoethanol resistant haemagglutinating antibody titres were determined in sera obtained from mice immediately after measuring the delayed type hypersensitivity reaction . Treatment with maximal erythromycin dose gave rise to a significant enhancement of the cellular immune response, and also to an acceleration of the humoral antibody response . On the other hand, treatment with minimal erythromycin dose gave rise to a slight depression of the immune cellular response and also to a depression of the antibody production at the beginning of the humoral response.

Can J Vet Res, 1989 Jan, 53(1), 48 - 51
Effect of adrenal blocking chemicals on viral and respiratory infections of chickens; Gross WB; In a series of experiments chickens were treated with chemicals which block the production of corticosterone by the adrenal cortex prior to being challenged with respiratory disease (and other) agents in order to determine if the course of the diseases could be altered . Some chickens received a single intramuscular injection (14 mg/kg) of 1,1-dichloro-2,2-bis/p-chlorophenyl/ethane (ABC) dissolved in corn oil (20 mg/mL) at least 12 h before challenge . Other chickens received feed containing 500 mg/kg of metyrapone for at least 12 h before and during the challenge infection . Treated chickens were more resistant than the untreated controls to Newcastle disease virus, Mycoplasma gallisepticum, combined M . gallisepticum-Newcastle disease virus infection, and avian adenovirus group II infection . The feeding of erythromycin (1 g/kg of feed), one day before and during the challenge, reduced the severity of M . gallisepticum infection . The effects of feeding both metyrapone and erythromycin resulted in a further increase in resistance . Chickens which had been treated with ABC had less severe lesions and greater postchallenge weight gain than the controls in response to a secondary Escherichia coli infection.

Drugs Exp Clin Res, 1989, 15(11-12), 527 - 33
Immunological and anti-inflammatory effects of clarithromycin: inhibition of interleukin 1 production of murine peritoneal macrophages; Takeshita K et al.; The immunological and anti-inflammatory effects of clarithromycin (CAM), a new oral macrolide antibiotic, were examined in in vitro models such as lymphocyte transformation (LTF) of murine spleen cells, interleukin 1 (IL-1) production of murine peritoneal macrophages and IL-1-induced proliferation of C3H/HeJ mice thymocytes; the results were compared with those achieved by erythromycin (EM) . CAM suppressed these responses much more than EM . Murine peritoneal macrophages precultured with CAM showed diminished IL-1 production, but macrophages precultured with EM did not, indicating that CAM has suppressive effects on the early phase of IL-1 production of murine peritoneal macrophages . Suppressive effects of CAM on IL-1 production by macrophages and proliferation of lymphocytes were independent of prostaglandin biosynthesis, since this drug had no effect on cyclooxygenase activity . Additional immunosuppressive and anti-inflammatory activities of CAM may explain its superior clinical effect.

Drugs Exp Clin Res, 1989, 15(9), 447 - 51
Efficacy and tolerability of combined topical treatment of acne vulgaris with tretinoin and erythromycin in general practice; Korting HC et al.; Efficacy and tolerability of a gel preparation with 0.025% tretinoin and 4% erythromycin in acne vulgaris was evaluated in an open multicentre study . A total of 1337 patients of either sex, aged 8 to 68 years, were enrolled in the study; 13 had to be excluded from analysis . Some 499 patients had received former acne treatment; this was described as non-efficient or poorly efficient in 90% of the patients . The treatment period lasted up to 14 weeks . Efficacy was determined by counting the acne lesions (comedones, papules and pustules) before drug administration and every second week during the treatment period . Lesions had diminished after 2 weeks in about 35% of the patients . At the end of the treatment period, comedones were eliminated in 47.0% and improved in another 41.4% . Papules were eliminated and improved in 58.2% and 32.6%, pustules in 74.3% and 18.3% respectively . Side-effects (erythema, burning, pruritus, scaling and dryness of the skin) occurred in 203 patients (15.3%) . Treatment was stopped in 25 subjects (1.9%) due to intolerance reactions . The results of the present study thus confirm the high efficacy and tolerability of the fixed combination observed previously in more selected patients . The fixed combination of tretinoin and erythromycin makes retinoic acid treatment possible even by a general practitioner.

Dermatol Monatsschr, 1989, 175(1), 40 - 3
{Local treatment of acne vulgaris with erythromycin}; Broniarczyk-Dyla G et al.; 2% Erythromycin solution was applied topically in 20 patients with papulopustular acne vulgaris . The treatment proved beneficial and its results were similar to those obtained in the group of patients who additionally received Erythromycin systemically.

J Chromatogr, 1988 Dec 29, 434(1), 177 - 86
Thin-layer chromatographic study of the metabolites of erythromycins in the Wistar rat; Kibwage IO et al.; The metabolites of erythromycin A, anhydroerythromycin A, N-demethylerythromycin A and erythromycin B in the Wistar rat were studied by thin-layer chromatography . In some experiments germ-free rats, rats with a cannulated bile duct and a gastrectomized rat were used . The erythromycins examined were shown to undergo two principal changes, N-demethylation and acid-catalysed degradation . It was demonstrated that the stomach and the liver are not the sole sites of acid degradation and demethylation of erythromycins, respectively . Erythromycin A gives three principal metabolites, anhydroerythromycin A, anhydro-N-demethylerythromycin A and N-demethylerythromycin A, and erythromycin A enol ether and N-demethylerythromycin A enol ether are present to a minor extent . 5-O-Desosaminylerythronolide A was also identified, suggesting the presence of an erythromycin glycosidase.

Arzneimittelforschung, 1988 Dec, 38(12), 1811 - 4
Effects of drugs on aminophylline elimination in rats; Szeitz A et al.; Effects of phenobarbital, phenytoin, carbamazepine, cimetidine, erythromycin, combination of sulfamethoxazole + trimethoprim (5:1), and rifampicin (rifampin) on the elimination of aminophylline were examined in female rats . Aminophylline was administered i.p . in a dose of 13.33 mg/kg . Blood samples were collected 0.5, 2, 4 and 7 h after the administration of the injection; one measurement was performed from one blood sample . Plasma aminophylline levels were measured by a modified HPLC method . The elimination half-life of the untreated control group (n = 27) was 4.62 h . The pretreatments with drugs examined were carried out by a gastric tube . The half-life of aminophylline after phenobarbital (10 mg/kg, 7 days, n = 29) was 2.09 h; after phenytoin (10 mg/kg, 7 days, n = 29), 2.47 h; after carbamazepine (400 mg/d, 7 days, n = 25), 2.19 h; after cimetidine (in cimetidine-treated group the blood samples were collected 0.5, 4 and 7 h after the aminophylline injection) (40 mg/kg, 7 days, n = 13), 1.77 h; after erythromycin (800 mg/d, 7 days, n = 28), 2.51 h; after the combination of sulfamethoxazole + trimethoprim in ratio of 5:1 (50 mg/kg, 7 days, n = 23), 2.85 h; and after rifampicin (300 mg/kg, 21 days, n = 23), 2.74 h . Sulfamethoxazole presumably interfered with the HPLC examination of aminophylline.(ABSTRACT TRUNCATED AT 250 WORDS)

Liver, 1988 Dec, 8(6), 350 - 3
Prolonged cholestasis and disappearance of interlobular bile ducts following chlorpropamide and erythromycin ethylsuccinate . Case of drug interaction?
Geubel AP, Nakad A, Rahier J, Dive C.
A 52-year-old man, having been treated for 4 months with chlorpropamide for diabetes mellitus type II, developed severe cholestatic hepatitis following a short course of erythromycin ethylsuccinate . Despite prompt withdrawal of both drugs, the cholestatic picture worsened and was associated with morphological evidence of disappearing interlobular bile ducts . After a 2-year course of profound cholestasis complicated by steatorrhea and striking hyperlipidemia, the patient died of ischemic cardiomyopathy . It is believed that this is the first published case of irreversible cholestasis with disappearance of ducts potentially related to a metabolic interaction between erythromycin ethylsuccinate and chlorpropamide.

Radiology, 1988 Dec, 169(3), 661 - 2
Erythromycin-induced hepatitis: simulator of malignancy; Rigauts HD et al.; A 67-year-old patient was admitted with a 2-week history of epigastric discomfort that began after an episode of upper respiratory tract infection treated with erythromycin . Results of liver function tests were abnormal . Abdominal ultrasound (US) and computed tomography showed multiple, poorly demarcated irregular lesions in both hepatic lobes, suggestive of diffuse metastatic invasion . Histologic examination of the biopsy specimen revealed drug-induced hepatitis . Ten weeks after withdrawal of the erythromycin, US showed complete resolution of the hyperechogenic liver lesions.

Biochim Biophys Acta, 1988 Nov 10, 951(1), 42 - 52
Action of erythromycin and virginiamycin S on polypeptide synthesis in cell-free systems; Chinali G et al.; Erythromycin (a 14-membered macrolide) and virginiamycin S (a type B synergimycin) block protein biosynthesis in bacteria, but are virtually inactive on poly(U)-directed poly(Phe) synthesis . We have recently shown, however, that these antibiotics inhibit the in vitro polypeptide synthesis directed by synthetic copolymers: this effect is analyzed further in the present work . We were unable to find any consistent alteration produced by these antibiotics on coupled and uncoupled EF-G- and EF-Tu-dependent GTPases, on the EF-Tu-directed binding of aminoacyl-tRNA to ribosomes, and on the EF-G- and GTP-mediated translocation of peptidyl-tRNA bound to poly(U,C).ribosome complexes . With these complexes, the peptidyl transfer reaction, as measured by peptidylpuromycin synthesis, was 10-30% inhibited by virginiamycin S and erythromycin . A direct relationship between the virginiamycin S- and erythromycin-promoted inhibition of poly(A,C)-directed polypeptide synthesis, on the one hand, and the EF-G concentration and the rate of the polymerization reaction, on the other hand, was observed, in agreement with a postulated reversible inhibitor action of these antibiotics . The increased inhibitory activity, which was observed during the first 4-6 rounds of elongation, in the presence of virginiamycin S or erythromycin, was suggestive of a specific action of these antibiotics on the correct positioning of peptidyl-tRNA at the P site . The marked stimulation of premature release of peptidyl-tRNA from poly(A,C).ribosome complexes can be referred to an altered interaction of the C-terminal aminoacyl residue of the growing peptidyl chain with the ribosome . We conclude that the action of virginiamycin S and erythromycin entails a template-dependent alteration of the interaction of peptidyl-tRNA with the donor site of peptidyltransferase, which may lead to a transient functional block of the ribosome and in some instances to a premature release of peptidyl-tRNA and termination of the elongation process.

Surgery, 1988 Nov, 104(5), 911 - 6
Acalculous hypersensitivity cholecystitis: hypothesis of a new clinicopathologic entity; Parry SW et al.; Acute acalculous cholecystitis is common, accounting for 5% to 10% of cases of acute cholecystitis . Although originally attributed to stasis and inspissated bile with subsequent obstruction of the cystic duct, acalculous cholecystitis has more recently been attributed to gallbladder ischemia from such conditions as hypotension or vasculitis . However, a significant number of cases of acute acalculous cholecystitis occur with no obvious cause . This report notes acute acalculous cholecystitis, diagnosed in 12 patients from 1982 to 1987, that was apparently precipitated by initiation of antibiotic therapy . Histologic sections of these gallbladders each disclosed a massive eosinophilic infiltrate . Two of the patients had identical signs, symptoms, and abnormal laboratory values during a previous course of erythromycin . These findings subsided when the antibiotic therapy was discontinued . We hypothesize that a significant cause of acute acalculous cholecystitis may be a hypersensitivity reaction to concurrent antibiotic therapy . Such patients should have antibiotic therapy halted or altered, which, it is hoped, will result in resolution of symptoms and avoidance of unnecessary laparotomy.

Z Geburtshilfe Perinatol, 1988 Nov-Dec, 192(6), 263 - 5
{When in pregnancy should screening for Chlamydia be carried out?}; Schlogl H et al.; One goal of every prenatal care should be the diagnosis of a cervical infection with Chlamydia trachomatis and the prevention of its transmission to the neonate . Therefore, we studied the questions (1) at which gestational age a screening would be most meaningful and (2) whether the woman's medical history, a vaginal smear or cervical cerclage suggests any risk of infection . 11 of 121 pregnant women (9.1%) had a positive test for cervical infection with Chlamydia trachomatis at their booking visit . More than half of them had a spontaneous remission at the follow-up visit . Practically, all newborns to infected mothers (at follow-up visits) had a positive test as well . We did not find any relationship between the medical history, vaginal smear or cervical cerclage and the incidence of Chlamydia trachomatis infection . In conclusion, we propose a screening for Chlamydia trachomatis infection of all pregnant women between the 34th and 38th week of gestation and treatment of infected individuals with erythromycin (4 x 500 mg t.i.d.).

J Antimicrob Chemother, 1988 Nov, 22(5), 605 - 12
Effects of erythromycin base and erythromycin esters on protein synthesis in vivo in Escherichia coli; Andersson SG et al.; The inhibitory effects on protein synthesis in vivo of erythromycin base and several erythromycin esters have been determined . An experimental method was used, especially suited for studies on short-lived antibiotics causing low levels of inhibition . Most of the tested derivatives were 2-3% as active as erythromycin base while a split product of erythromycin, anhydroerythromycin, was 4% as effective.

J Biol Chem, 1988 Oct 15, 263(29), 14992 - 5
Purification of thymidine-diphospho-D-glucose 4,6-dehydratase from an erythromycin-producing strain of Saccharopolyspora erythraea by high resolution liquid chromatography; Vara JA et al.; TDP-D-glucose 4,6-dehydratase was purified from Saccharopolyspora erythraea, the producer of the macrolide antibiotic erythromycin A, by a high resolution chromatographic method that exploited the difference in the behavior of the protein on anionic exchange chromatography in Tris/HCl or phosphate buffers . By this method, the enzyme was purified approximately 900-fold by two anionic exchange steps to more than 90% homogeneity . It was further purified to apparent homogeneity by hydrophobic interaction chromatography . The enzyme is a homodimer of Mr 36,000 subunits, is highly specific for TDP-D-glucose, requires NAD+ as cofactor, and shows a K'm of 34 microM and V'max of 26 mumol h-1 mg-1 of protein for TDP-D-glucose . TDP and TTP strongly inhibit the enzyme at 2 mM . The maximal TDP-D-glucose 4,6-dehydratase activity coincides with the time of erythromycin production, suggesting that this enzyme is involved in antibiotic biosynthesis.

Arch Dermatol, 1988 Oct, 124(10), 1545 - 9
Mycobacterium avium-intracellulare infection associated with hairy-cell leukemia; Maurice PD et al.; A 66-year-old man with hairy-cell leukemia was treated successfully with interferon alfa, with normalization of his hematologic parameters . After 2.5 months he became ill again and, following extensive investigation, Mycobacterium avium-intracellulare grew from a bone marrow specimen . Although initiation of quadruple antituberculous chemotherapy resulted in an improvement of his general condition, after two months he started to develop widespread cutaneous and subcutaneous nodules, biopsy of which showed appearances compatible with mycobacterial infection . Over the next two months the skin lesions progressed slowly so erythromycin, to which in vitro testing showed the organism to be sensitive, was added to his therapy . This resulted in a marked improvement of all skin lesions . This case is the first to be reported of disseminated atypical mycobacterial infection in a patient receiving interferon treatment for hairy-cell leukemia.

Pharmacol Toxicol, 1988 Oct, 63(4), 215 - 20
No effect of roxithromycin on pharmacokinetic or pharmacodynamic properties of warfarin and its enantiomers; Paulsen O et al.; The macrolide antibiotics are metabolized by cytochrome P-450 enzymes in the liver and interactions with similarly metabolized compounds have been described . Simultaneous treatment with erythromycin and warfarin is known to decrease warfarin clearance and prolong prothrombin time . Roxithromycin (RU 28965), a new erythromycin derivative with improved pharmacokinetic properties, might then, because of structure similarity, be expected to interact with warfarin . In 21 healthy volunteers, the effect of orally administered roxithromycin (150 mg b.i.d.) on warfarin steady-state kinetics, and the effects of warfarin on roxithromycin kinetics, were investigated in a double-blind, randomized study versus placebo . Since the warfarin enantiomers, R- and S-warfarin have both different potency and different metabolism, the ratio between the enantiomers with and without roxithromycin, was also determined . In this study, mean AUC for warfarin increased slightly from day 14 of warfarin treatment to day 28, but no difference was found between the roxithromycin group and the placebo group, and no change appeared in the ratio between the warfarin enantiomers . A moderate increase in dosage was needed to maintain hypocoagulability during warfarin medication, but there was no difference between the roxithromycin group and the placebo groups, respectively . In addition, roxithromycin kinetics appeared to be unaffected by warfarin treatment.

Antimicrob Agents Chemother, 1988 Oct, 32(10), 1541 - 6
Toxicity, uptake, and subcellular distribution in rat hepatocytes of roxithromycin, a new semisynthetic macrolide, and erythromycin base; Villa P et al.; Rat hepatocytes were used to study the toxicity of a new semisynthetic macrolide, roxithromycin, in comparison with erythromycin base and erythromycin estolate . Roxithromycin caused lactate dehydrogenase leakage close to that of erythromycin estolate and higher than erythromycin base after 21 h of exposure to the drugs . This effect was, at least in part, explained by the higher uptake: roxithromycin was two to three times more concentrated by liver cells than erythromycin base . For both roxithromycin and erythromycin base, the uptake depended on time, temperature, and extracellular antibiotic concentration . The accumulated macrolides egressed rapidly when cells were incubated in antibiotic-free medium . No uptake and no loss of accumulated drugs were observed at 4 degrees C . After accumulation by hepatocytes, roxithromycin and erythromycin base underwent similar subcellular distribution, mostly concentrating in cytosol and lysosomes . The small amount accumulated in the other particulate fractions followed the order mitochondria much greater than nuclei greater than microsomes . Roxithromycin, however, was less concentrated than erythromycin base in the microsomes.

J Clin Gastroenterol, 1988 Oct, 10(5), 551 - 4
Erythromycin-induced dynamic ileus?
Heyman SN, Stalnikowicz R, Heyman A, Gilon D, Mogle P.
A 39-year-old man and a 79-year-old woman developed dynamic ileus soon after erythromycin stearate was administered for a respiratory tract infection . Both had had prior uncomplicated abdominal operations: the man, vagotomy and pyloroplasty for bleeding duodenal ulcer, 3 years earlier; and the woman, an appendectomy some 44 years before . The temporal association with erythromycin therapy, resolution of signs and symptoms when the drug was stopped, an uneventful recovery, and the absence of other causes, suggest a possible role of erythromycin in the pathogenesis of dynamic ileus in these patients . Disturbed gastrointestinal motility patterns caused by erythromycin, in the presence of structural changes of the alimentary tract due to prior surgical procedures, may have contributed and we review these events.

Dermatol Clin, 1988 Oct, 6(4), 575 - 84
New drugs for dermatologic diseases; Landow RK; Since its isolation less than 20 years ago, cyclosporine has become one of the major drugs in the armamentarium of transplant surgeons . A serendipitous event in 1979 suggested the drug might offer significant benefits in patients with psoriasis . Multiple trials have subsequently confirmed its usefulness in psoriasis at steadily decreasing dosages . Administered orally, the drug must be taken in a ritualistic fashion as it tends to sequestrate on the sides of the glass . A routine determination of blood levels becomes important in order to maintain the peak and trough concentrations within a relatively narrow window of safety . Depending on the particular assay used, significant differences in concentrations appear, making knowledge of the laboratory's normal values essential . Blood levels of cyclosporine vary with multiple drugs, including erythromycin, prednisone, and ketoconazole . The drug acts principally via its interference with the function of the helper T lymphocytes . Clofazimine (Lamprene) offers another weapon, especially for therapy of resistant pustulosis of the palms and soles.

Clin Pharmacokinet, 1988 Oct, 15(4), 227 - 44
Pharmacokinetic interactions with digoxin; Rodin SM et al.; Numerous pharmacological agents have been shown to produce clinically significant pharmacokinetic interactions with digoxin . Drugs which reduce digoxin absorption include the antacids aluminium hydroxide, magnesium hydroxide and magnesium trisilicate, the antidiarrhoeals kaolin and pectin, the hypocholesterolaemic agent cholestyramine and the chemotoxins cyclophosphamide, vincristine and bleomycin . Certain antibiotics including sulphasalazine, neomycin and aminosalicylic acid reduce digoxin absorption while others, including erythromycin and tetracycline, increase the bioavailability of digoxin in some patients . Capsule preparations of digoxin in solution are less subject to several of the interactions which affect the absorption and bioavailability of digoxin tablets . Various drugs induce alterations in the volume of distribution and clearance of digoxin . Cardiac patients receiving digoxin therapy are particularly prone to interactions with commonly co-administered medications such as the antiarrhythmics quinidine and amiodarone, the calcium channel blockers verapamil and nifedipine, and possibly some vasodilating agents . Studies of digoxin interactions have yielded discrepant results, indicating the need for careful analysis of investigational design before arriving at clinical conclusions.

Cutis, 1988 Oct, 42(4), 311 - 2
An unanticipated use of a topical cream; Lazar AP et al.; A sixteen-year-old black male, distraught over his acne, injected his face via syringe and needle with a topical cream . Within twelve hours, the injected lesions became red and edematous, and later tender . After treatment with oral prednisone and erythromycin, the lesions resolved . This case serves to illustrate the unexpected misuses of cosmetics, in this instance, a patient anxious only to improve his acne problem.

J Am Acad Dermatol, 1988 Sep, 19(3), 431 - 42
Use of oral and topical agents for acne in pregnancy; Rothman KF et al.; Dermatologists frequently are consulted by a pregnant patient or a woman of childbearing age who desires acne therapy . Because there are no published studies in which women took acne medications throughout pregnancy, information about safety must be obtained indirectly from studies in which the agents were taken for another indication during some portion of pregnancy . Oral tetracycline is associated with maternal liver toxicity and deciduous tooth staining in the infant, and tetracycline occasionally has been associated with other congenital anomalies . Maternal isotretinoin ingestion is associated with major craniofacial and cardiac deformities, as well as other congenital anomalies . Erythromycin, however, appears to be safe . Topical acne medications never have been implicated as a cause of fetal deformities in human beings . Dermatologists should be aware of potential toxic and teratogenic effects of acne medicines before prescribing them to women of childbearing age . Prompt reporting of adverse effects is encouraged.

Toxicology, 1988 Aug, 50(3), 283 - 301
Induction of the rat hepatic microsomal mixed-function oxidases by 3 imidazole-containing antifungal agents: selectivity for the cytochrome P-450IIB and P-450III families of cytochromes P-450; Rodrigues AD et al.; Administration of the imidazole antifungal agents ketoconazole, miconazole and clotrimazole gave rise to increases in the microsomal cytochrome P-450 levels and the NADPH-dependent reduction of cytochrome c . Clotrimazole, and to a much lesser extent miconazole and ketoconazole, stimulated the dealkylation of pentoxyresorufin . All 3 agents gave rise to small, but significant increases in the O-deethylation of ethoxycoumarin and ethoxyresorufin . The antifungal-induced O-deethylation of ethoxycoumarin was much more sensitive to inhibition by metyrapone rather than by alpha-naphthoflavone . The binding of metyrapone to reduced microsomes was enhanced by treatment of animals with the 3 antifungal agents, clotrimazole being clearly the most potent . Immunoquantitation of cytochrome P-450 proteins using an ELISA procedure and employing anti-cytochrome P-450c (P-450IA1, P-448 low spin) and P-450b (P-450IIB1) antisera revealed that clotrimazole and miconazole, but not ketoconazole, induced the levels of phenobarbital-induced cytochromes P-450, while none of the antifungal agents increased the levels of cytochrome of P-448 proteins . Similar results were obtained using Western blots employing the above antibodies . On SDS-polyacrylamide gel electrophoresis microsomes derived from animals pretreated with clotrimazole showed intensification of a band at 51 kDa which was identified by Western blotting as the PCN-inducible form of cytochrome P-450 (cytochrome P-450p, P-450III family) . Similar, but less pronounced intensification was seen with microsomes from animals pretreated with miconazole and ketoconazole . Furthermore, microsomes from clotrimazole- and ketoconazole-treated animals interacted with erythromycin to yield type I spectra . It is concluded that the imidazole-containing agents clotrimazole and miconazole, and to a much lesser extent ketoconazole, are potent inducers of the rat hepatic microsomal mixed-function oxidases, displaying selectivity towards the P-450IIB (phenobarbital-inducible) and P-450III (PCN-inducible) families of cytochrome P-450 proteins.

Genitourin Med, 1988 Aug, 64(4), 247 - 8
Pivampicillin compared with erythromycin for treating women with genital Chlamydia trachomatis infection; Cramers M et al.; In a randomised single blind study, pivampicillin was compared with erythromycin in women with urogenital Chlamydia trachomatis infections . The pivampicillin dosage was 700 mg twice a day and the erythromycin dosage 500 mg twice a day for seven days . Follow up took place on days 7 and 14 after the start of treatment . All 26 women treated with pivampicillin were culture negative for chlamydiae at the first and second follow up visits . All 23 women who received erythromycin were culture negative at the first follow up visit, but one was culture positive at the second follow up visit . Gastrointestinal side effects were recorded in five patients receiving pivampicillin and in nine receiving erythromycin . Two patients receiving erythromycin were withdrawn from treatment because of gastrointestinal disturbances, compared with none receiving pivampicillin.

Arch Mal Coeur Vaiss, 1988 Aug, 81(8), 1001 - 8
{Electrophysiological study of pro-arrhythmogenic effects of erythromycin}; Ponsonnaille J et al.; Three cases of torsades de pointe induced by erythromycin have recently been reported . After observing a new case, the authors tried to demonstrate the possible mechanism of the arrhythmogenic action of this molecule . Twenty-two patients undergoing electrophysiological studies in the catheter laboratory to determine the cause of syncope were given an intravenous injection of 10 mg/Kg of erythromycin lactobionate . The drug was injected in 1 minute (bolus) in 11 patients (Group A) . The other 11 patients (Group B) received the drug by slow intravenous infusion (20 minutes) . Electrophysiological parameters were measured before and after erythromycin . A significant prolongation of the atrial refractory periods (+39 ms), ventricular refractory periods (+20 ms), QT (+20 ms) and QTC intervals (+42 ms) was observed in Group A . These electrophysiological effects could explain an arrhythmogenic action similar to that of antiarrhythmic drugs in Group I of Vaughan-Williams' classification . The slow intravenous infusion of erythromycin in Group B considerably reduced these undesirable secondary effects . This difference was directly related to serum concentrations of the molecule.

Agents Actions, 1988 Aug, 25(1-2), 124 - 31
Comparative studies on the effects of erythromycin A and azithromycin upon extracellular release of lysosomal enzymes in inflammatory processes; Carevic O et al.; In the present studies the in vivo and in vitro effects of erythromycin A and azithromycin, a new type of macrolide (Fig . 2.), were investigated upon extracellular release of lysosomal enzymes, beta-glucuronidase (beta-Gluc) and beta-N-acetylglucosaminidase (beta-Glm) by using two experimental model systems: in vivo-adjuvant-induced arthritis in rats and in vitro- human polymorphonuclear leucocytes (PMNL) exposed to bovine serum albumin/anti-bovine serum albumin (BSA/anti-BSA), immune complex . Administrations of erythromycin A or azithromycin at doses of 5, 10 and 15 mg/kg into rats one day prior and 2, 4, 6, 8 and 10 days after a single subplantar injection of Freund's complete adjuvant significantly (p less than 0.01) inhibited extracellular release of lysosomal enzymes tested in the synovial fluid of injected left hind paw . These effects were dose-dependent . Further, erythromycin A and azithromycin at concentrations of 10(-7) M, 10(-6) M and 10(-5) M significantly (p less than 0.01) reduced excocytosis of both lysosomal enzymes, beta-Gluc and beta-Glm from human PMNL initiated by BSA/anti-BSA in a dose-related fashion . However, azithromycin was by far more effective (p less than 0.01) in decreasing extracellular release of beta-Gluc and beta-Glm either in the in vivo or in vitro experiments in comparison with erythromycin A . Appropriate control experiments excluded the possibilities that erythromycin A or azithromycin interfered with activities of lysosomal enzymes or with test reagents . Also, in no instances was there enhanced release of a cytoplasmic enzyme LDH.(ABSTRACT TRUNCATED AT 250 WORDS)

J Fam Pract, 1988 Jul, 27(1), 57 - 61
Theophylline dosing and theophylline level testing in a family practice population; Moore LD 3rd et al.; Theophylline level testing enables the physician to monitor patients on theophylline and maintain benefit vs risk at an optimum ratio . This study consisted of a retrospective chart review of 53 patients who had a total of 103 serum theophylline level determinations (STLDs) over a 12-month period . The study was designed to look at reasons why physicians ordered STLDs and to what extent those results influenced subsequent theophylline prescribing . Findings showed that a large number of STLDs were ordered on asymptomatic patients with no recent dose change or initiation of therapy and no recent hospitalization or emergency room visit . The most common reason for ordering an STLD was presentation with symptoms or signs of asthma and no other recent events . On several occasions when low results were obtained, theophylline dosage was not increased . In some of these cases the patient's clinical presentation may have influenced the decision to maintain the same dosage . Use of erythromycin and smoking status were observed to affect theophylline clearance . Most physicians failed to document time of last theophylline dose, which hindered accurate interpretation of STLDs.

Antimicrob Agents Chemother, 1988 Jul, 32(7), 1019 - 24
Concentrations of erythromycin, 2'-acetyl erythromycin, and their anhydro forms in plasma and tonsillar tissue after repeated dosage of erythromycin stearate and erythromycin acistrate; Gordin A et al.; The concentrations of erythromycin, 2'-acetylerythromycin (2'-AE) and their anhydro forms in plasma and tonsillar tissue were analyzed after a 3-day repeated-dosage regimen of erythromycin stearate (ES; 500 mg twice a day {b.i.d}) and erythromycin acistrate (EA), a new erythromycin prodrug, at two doses (400 and 500 mg b.i.d.) . The tonsils of 40 patients were removed at 112 to 329 min after intake of the last dose . Blood samples were collected at the time of tonsillectomy and at 0, 2, and 6 h after the last dose . At all time points, EA produced severalfold more total antibiotic (erythromycin + 2'-AE) concentrations in plasma compared with ES . There were two nonabsorbers in the ES group, but none in the two EA groups . The mean total antibiotic levels in tonsillar tissue after EA treatment exceeded the levels after treatment with ES by a factor of 3 (for EA at 400 mg b.i.d.) and 4.5 (for EA at 500 mg b.i.d.) . The ratios of erythromycin concentration in tonsil to that in plasma at the time of tissue removal were quite similar for all groups (means, 0.51 to 0.54) . In the EA groups, 2 of 26 (8%) patients had no measurable erythromycin in the tonsillar tissue samples, whereas in the ES group, 3 of 14 (21%) patients had no measurable erythromycin in the same tissue . The degree of hydrolysis of 2'-AE to erythromycin was about 25% in plasma at the time of tonsillectomy for both EA groups and about 40% in tonsillar tissue . There were negligible amounts of anhydro forms in plasma after EA administration, whereas in the ES group, anhydroerythromycin levels were, from time to time, even higher than erythromycin levels . Very high levels of anhydro forms were detected in tonsillar tissue after ES treatment, whereas only low levels were found after EA administration.

J Antimicrob Chemother, 1988 Jul, 22 Suppl B, 69 - 72
Comparison of spiramycin and erythromycin in the treatment of experimental guinea pig legionellosis; Dournon E et al.; Spiramycin was compared with erythromycin in a guinea pig model of severe Legionella pneumophila serogroup 1 infection . Male guinea pigs weighting 264-321 g were infected by the intraperitoneal route with 1.2 x 10(7) virulent L . pneumophila serogroup 1 . Forty eight h after infection, animals that had lost greater than or equal to 9% of their body weight were randomly assigned to receive 48, 54 and 72 h after infection intraperitoneal injections of (1) distilled water (n = 20), (2) erythromycin lactobionate, 30 mg/kg per injection, (n = 22) or (3) the injectable form of spiramycin adipate, 30 mg/kg per injection (n = 22) . Animals were observed daily for 15 days . All infected animals treated with distilled water died within four days of infection . Of the 22 animals treated with spiramycin, 10 (45.5%) died, and of the 22 animals treated with erythromycin, 11 (50.0%) died of disseminated L . pneumophila infection . In this animal model of very severe L . pneumophila infection, the injectable forms of erythromycin and of spiramycin gave similar results . Spiramycin should therefore be considered for the treatment of Legionnaires' disease in man.

J Antimicrob Chemother, 1988 Jul, 22 Suppl B, 179 - 82
Efficacy of intravenous spiramycin in the treatment of severe Legionnaires' disease; Mayaud C et al.; Spiramycin is a 16-membered macrolide that has been shown in cell and animal models to be active against Legionella spp . The activity of the injectable form of spiramycin was evaluated in the treatment of severe Legionnaires' disease in seven immunocompromised and three previously healthy patients . Seven of the ten patients were cured . Three patients died primarily from the underlying disease or from intercurrent complications . This result and the better tolerance of spiramycin compared with 14-membered macrolides suggest that spiramycin may be a suitable alternative to erythromycin for the treatment of Legionnaires' disease.

Jpn J Antibiot, 1988 Jul, 41(7), 836 - 40
Rokitamycin uptake by alveolar macrophages; Tasaka Y et al.; The ability of antibiotics to enter cells, especially phagocytic cells, may be an important factor affecting therapy for infections caused by organisms which survive and proliferate intracellularly . It is well known that macrolides and clindamycin have high intracellular penetration ability . We studied the uptake of rokitamycin (RKM), a new oral macrolide, using rabbit alveolar macrophages and 2 other macrolides for comparison . Intracellular concentrations of erythromycin and josamycin were, respectively, approximately 20 and 40 times higher than extracellular concentrations when they were incubated at an initial extracellular concentration of 5 micrograms/ml (I/E = 20.1 +/- 2.6, 40.8 +/- 7.4) . In comparison to these 2 macrolides, the uptake of RKM was massive and very rapid . The cellular concentration of RKM was approximately 120 times higher than the extracellular concentration . Uptake of the 3 macrolides by rabbit alveolar macrophages at 4 degrees C was approximately 10% of that at 37 degrees C . This study demonstrated that RKM was rapidly and massively accumulated by alveolar macrophages, and that the drug accumulation depends on temperature . These observations suggest that RKM therapy may be very effective for the treatment of some infectious diseases.

Jpn J Antibiot, 1988 Jul, 41(7), 830 - 5
{A study of antichlamydial effect of rokitamycin}; Soejima R et al.; MICs of a new macrolide antibiotic, rokitamycin (RKM), for Chlamydia psittaci and Chlamydia trachomatis were determined . Meanwhile, the organisms were observed under the electron microscope for morphologic changes with the addition of RKM . 1 . MICs of RKM for C . psittaci MP and 3 strains of C . psittaci isolated from budgerigars kept by patients ranged from 0.05 to 0.10 microgram/ml, and those for 3 strains of C . trachomatis B, E and L2 ranged from 0.20 to 0.39 microgram/ml . These MICs were higher than MICs of minocycline (MINO), doxycycline and rifampicin, but lower than MICs of erythromycin and midecamycin against these organisms . 2 . The addition of MINO or RKM to C . psittaci Izawa and C . trachomatis L2 at concentrations twice as high as MICs resulted in no formation of elementary body or intermediate form inside the inclusion body, and abnormal enlargement of reticulate body containing irregularly distributed cytoplasmic components.

Jpn J Antibiot, 1988 Jul, 41(7), 823 - 9
{Effect of rokitamycin on upper gastrointestinal contractile activity . Analysis of side-effects on gastrointestinal tract}; Itoh Z; In order to determine whether rokitamycin (RKM), one of the macrolide antibiotics, has any side effects on the gastrointestinal tract, the effect of intraduodenal administration of RKM (1.0, 3.0 and 9.0 mg/kg) on gastrointestinal contractile activity was studied by means of force transducers implanted chronically on the gastric body, gastric antrum, duodenum and upper jejunum in conscious dogs . Erythromycin (EM 0.3, 1.0 and 3.0 mg/kg) and kitasamycin (LM 1.0, 3.0 and 9.0 mg/kg), both macrolide antibiotics, were used as control drugs . RKM, when given at 3.0 mg/kg and 9.0 mg/kg doses, induced segmentation contractions only in the duodenum where it was administered . The duration of the RKM-induced contractions was 7.5 +/- 2.5 minutes for 3.0 mg/kg and 15.8 +/- 3.0 minutes for 9.0 mg/kg, and the contractile force of the contractions was 43 to 82% of the maximum contractile force of the interdigestive contractions in the duodenum . EM, at 0.3 mg/kg, evoked a series of strong contractions quite different from those induced by RKM but similar to the natural interdigestive contractions, and with large doses, dose-dependent long-lasting interdigestive contractions were induced . On the other hand, LM did not stimulate notable gastrointestinal contractile activity even at a 9.0 mg/kg dose . In order to eliminate the possibilities of the contraction being caused by the effect of RKM on the duodenum through the general circulation upon absorption, 3.0 mg/kg RKM was given intravenously . It was found that intravenous injection of RKM did not evoke any contractions attributable to the direct action of RKM in the circulation.(ABSTRACT TRUNCATED AT 250 WORDS)

Arch Surg, 1988 Jul, 123(7), 895 - 900
A new bowel preparation for elective colon and rectal surgery . A prospective, randomized clinical trial; Wolff BG et al.; A two-day cathartic/enema preparation with oral administration of erythromycin and neomycin was compared with an orthograde lavage preparation with oral administration of metronidazole and neomycin in a prospective randomized trial in 300 and 293 eligible patients, respectively, who were undergoing elective colon and rectal surgery . Patients were assessed for infections at six weeks after discharge from the hospital . The major infection rate was less than 1% and the minor infection rate was less than 4% . The overall infection rate was 4.2% . The type of bowel preparation used, the type of operation, and the addition of systemic antibiotic therapy did not affect infection rates significantly . We conclude that this one-day lavage technique, as described, is a safe, effective, economical, and preferred method of colonic preparation for elective colon and rectal surgery.

Pediatr Med Chir, 1988 Jul-Aug, 10(4), 395 - 400
{Amoxicillin-clavulanic acid combination in bacterial infections of the upper respiratory tract in childhood . Controlled clinical study}; Boccazzi A et al.; A comparative clinical trial of amoxycillin - clavulanic acid combination versus erythromycin was carried out in a case series of 20 pediatric patients, suffering from upper respiratory tract infections with a proven bacterial etiology and different localization (tonsils, nasal and paranasal sinuses and ear) . The results have confirmed the highly innovative efficacy of amoxycillin - clavulanic acid combination: the clinical judgement was in fact favourable, with eradication of the pathogenic agent in 90% of cases . The tolerability of the combination was globally good from both the general and local point of view.

J Antimicrob Chemother, 1988 Jul, 22 Suppl B, 207 - 10
Spiramycin: safety in man; Descotes J et al.; Spiramycin, a 16-membered lactone ring macrolide, has been in clinical use for the past 15 years with little serious associated toxicity . Gastrointestinal disturbance has usually been mild and no changes in gastrointestinal motility have been noted either experimentally or in humans, in contrast to other macrolides, such as erythromycin . Allergic reactions have been uncommon and mainly restricted to transient skin eruptions . Although liver injury is a possible complication of most macrolide treatments, no conclusive evidence for spiramycin-induced hepatitis is currently available, and, again in contrast to most other macrolides, the lack of drug interactions with spiramycin has been clearly established in biochemical, pharmacokinetic and clinical studies.

J Antimicrob Chemother, 1988 Jul, 22 Suppl B, 201 - 6
Macrolides and gastrointestinal motility; Pilot MA et al.; Erythromycin was the first macrolide used clinically, and it is still the most widely prescribed in spite of reports of gastrointestinal side-effects . Erythromycin was given iv or orally to fasted and fed dogs with sensors implanted on the gastrointestinal tract for the measurement of motility . There was a large increase in stomach and upper small bowel contractile activity, accompanied by nausea and vomiting, while the distal small bowel appeared inhibited . Similar effects were seen in man . By contrast, two 16-membered macrolides, spiramycin and josamycin, did not produce such side-effects when given either orally or intravenously to dogs.

J Antimicrob Chemother, 1988 Jul, 22 Suppl B, 183 - 7
The efficacy and safety of spiramycin in the treatment of nongonococcal urethritis in men; Segev S et al.; Twenty-five male patients with nongonococcal urethritis including 15 chlamydial infections, were treated with spiramycin for ten days . All but four patients had been treated previously, mostly with tetracyclines . Chlamydia trachomatis was cultured in seven patients and was detected in three additional men by immunofluorescent smear . Five other patients had antibodies to chlamydia, and one patient yielded a positive culture for Ureaplasma urealyticum and Mycoplasma hominis . A successful clinical response was observed in 64% of the patients; C . trachomatis was eradicated from six of seven patients with positive cultures and the three positive direct smears were negative after treatment . It is concluded that spiramycin can be used effectively for the therapy of acute nongonococcal urethritis, as well as in patients who have failed to respond to previous treatment with tetracyclines and erythromycin.

J Antimicrob Chemother, 1988 Jul, 22 Suppl B, 159 - 63
Comparison of spiramycin with erythromycin for lower respiratory tract infections; De Cock L et al.; The efficacy and safety of 2 g oral spiramycin daily were compared with those of 2 g of oral erythromycin daily in a multicentre open prospective trial, involving 198 patients, with a mean age of 61.75 years, with a clinical and radiological diagnosis of acute lower respiratory tract infection . The diagnoses were: acute bronchitis (96), acute superinfection of chronic bronchitis (60) and pneumonia (42) . The patients were assessed before therapy and after three and ten days of therapy . Seventy-four (76.3%) of the patients were cured in the spiramycin group and 64 (63.4%) were cured in the erythromycin group (P less than 0.05) . Significantly more patients complained of side effects in the erythromycin group (41.4%) than in the spiramycin group (11.8%) P less than 0.001.

J Antimicrob Chemother, 1988 Jul, 22 Suppl B, 141 - 4
The spiramycin paradox; Smith CR; Spiramycin has been found to be effective in a variety of clinical and experimental infections despite modest in-vitro activity . In animal models of infection, spiramycin has been found to be as effective as or more effective than erythromycin despite inferior in-vitro activity . These paradoxical results are explained in part by spiramycin's ability to achieve intra-cellular and tissue concentrations that exceed serum concentrations by a factor of ten or more . Furthermore, spiramycin clearance from these sites is much lower resulting in sustained tissue and intracellular concentrations . Finally, spiramycin appears to produce a substantial post-antibiotic effect and, possibly, subinhibitory effects that may further enhance its in-vivo activity.

Thorax, 1988 Jun, 43(6), 488 - 9
Pulmonary Mycobacterium kansasii infection successfully treated with a regimen containing erythromycin; Guest PJ et al.; We report a case in which erythromycin was used in place of rifampicin after a severe reaction to the latter in the treatment of pulmonary Mycobacterium kansasii infectionPublication Types:

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