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Some properties of two erythromycin-dependent strains of Escherichia coli.

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.

Aminoglycosides↗

Generation of an erythromycin-sensitive derivative of Clostridium difficile strain 630 (630Deltaerm) and demonstration that the conjugative transposon Tn916DeltaE enters the genome of this strain at multiple sites.

Erythromycin resistance in Clostridium difficile strain 630 is conferred by a genetic element termed Tn5398 which contains two erm(B) genes: erm1(B) and erm2(B). An erythromycin-sensitive derivative of strain 630 (designated 630Deltaerm) was generated by spontaneous mutation after continuous subculture for 30 days. This strain had lost the erm2(B) gene from within Tn5398 but retained erm1(B). However, the strain could revert to erythromycin resistance at a frequency of 2.79 x 10(-8), although it still contained the deletion of erm2(B). The availability of C. difficile 630Deltaerm allowed the behaviour of Tn916DeltaE to be investigated in this strain. This element entered the genome at multiple sites indicating that it could be useful as an insertional mutagen.

Blotting, Southern↗

Biliary excretion of erythromycin after parenteral administration.

1 The biliary excretion of erythromycin has been studied following parenteral administration in 23 patients. 2 Mean bile levels of the drug were approximately ten times higher than corresponding serum concentrations 1 h after i.v. (erythromycin lactobionate) and i.m. (erythromycin ethylsuccinate) injection. 3 Thus, unlike many antimicrobial agents, these compounds are well concentrated in the bile.

Bile↗

Inhibition by erythromycin of the conversion of carbamazepine to its active 10,11-epoxide metabolite.

The serum levels of carbamazepine (CBZ) and its 10,11-epoxide metabolite (CBZ-E) were determined in seven subjects after a single dose of CBZ (400 mg) in the control state and during co-administration of erythromycin (500 mg three times daily for 10 days). Erythromycin treatment was associated with a decrease in CBZ clearance and a prolongation of CBZ half-life, while CBZ-E levels were markedly reduced. These data provide evidence that erythromycin inhibits the conversion of CBZ to its epoxide metabolite.

Adult↗

Lack of effect of erythromycin on the pharmacokinetics of single oral doses of phenytoin.

The effect of erythromycin on the pharmacokinetics of phenytoin was studied in eight healthy volunteers using a balanced randomised cross-over design. Volunteers received a single oral dose of 400 mg of phenytoin sodium during each phase. During the treatment phase, the phenytoin sodium dose was administered 4.5 days after the commencement of a 7 day course of erythromycin base (250 mg every 6 h). There was no significant difference between the control and treatment phases (P greater than 0.05) with respect to the area under the plasma phenytoin concentration-time curve, the fraction of phenytoin unbound in plasma, the area under the unbound phenytoin concentration-time curve, the elimination half-life of phenytoin or the fraction of the dose excreted in urine as free and conjugated hydroxyphenylphenylhydantoin. This single dose study indicated that the intrinsic clearance of unbound phenytoin was unaffected by the concurrent administration of erythromycin.

Administration, Oral↗

Cyclosporin-erythromycin interaction in renal transplant patients.

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.

Administration, Oral↗

Benzoyl peroxide versus topical erythromycin in the treatment of acne vulgaris.

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

Acne Vulgaris↗

Molecular characterization of a gene from Saccharopolyspora erythraea (Streptomyces erythraeus) which is involved in erythromycin biosynthesis.

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.

Amino Acid Sequence↗

Changes in the prevalence of subgingival enteric rods, staphylococci and yeasts after treatment with penicillin and erythromycin.

The changes in the balance of microbial flora in the periodontium after antibiotic treatment were investigated in a blind study. The prevalence of gram-negative enteric rods, staphylococci and yeasts was followed before and during penicillin or erythromycin treatment of 72 periodontitis patients without periodontal cleaning. The prevalence of subgingival coagulase-positive staphylococci increased significantly following systemic penicillin therapy. After systemic erythromycin therapy, the prevalence of subgingival gram-negative enteric rods increased. Ten of 24 (42%) patients receiving systemic penicillin therapy developed clinical evidence of periodontal abscesses. In the absence of conventional mechanical cleaning, systemic administration of penicillin and erythromycin antibiotic to patients with pre-existing periodontitis may lead to periodontal superinfection with opportunistic organisms.

Adult↗

In vitro antimicrobial susceptibility of periodontopathic Actinobacillus actinomycetemcomitans to roxithromycin and erythromycin.

The in vitro minimal inhibitory concentrations (MIC) and minimal bactericidal concentration (MBC) of roxithromycin and erythromycin against Actinobacillus actinomycetemcomitans were evaluated. Sixty-seven different A. actinomycetemcomitans isolated from periodontal pockets of 101 subjects with different forms of early-onset and adult periodontitis and three reference strains of A. actinomycetemcomitans (ATCC 29522, ATCC 29523, and NCTC 9710) were included in this study. Erythromycin showed poor in vitro activity against A. actinomycetemcomitans; roxithromycin, on the contrary, exhibited good in vitro activity. Moreover, roxithromycin showed the best in vitro antimicrobial activity against 17 serotype a and 12 serotype c subpopulations of A. actinomycetemcomitans; against 38 serotype b subpopulation of A. actinomycetemcomitans, roxithromycin was consistently active. Roxithromycin exhibited MBC values usually equal to, or one-fold higher than MIC values. All the MBC values of erythromycin were three- to four-fold higher than the respective MIC result. Since roxithromycin is characterized by high concentrations in serum and good penetration and diffusion into gingival tissue, it could be expected to pass into the gingival crevicular fluid at levels sufficiently high to inhibit A. actinomycetemcomitans in vivo. These data indicate that roxithromycin might be a potential candidate for therapeutic trials in patients with A. actinomycetemcomitans-associated periodontitis.

Adolescent↗

Increasing erythromycin resistance among group A streptococci causing tonsillitis in a tertiary care hospital in southern India.

Group A streptococci (GAS) (n = 1313) isolated from patients with clinical symptoms of pharyngitis or tonsillitis attending a tertiary care hospital in southern India during 1986-2002 were tested for susceptibility to penicillin and erythromycin. The overall erythromycin resistance rate was 2.7% (n = 36). During 1986-1993, erythromycin resistance was observed in only one (2%) isolate in 1987, but reappeared in 1994 (2.7%), increased to 5.8% in 1999, and reached a maximum frequency of 13.8% in 2002. All isolates were susceptible to penicillin. The data indicate the need for continued surveillance of susceptibility patterns among GAS isolates in order to monitor the development of antibiotic resistance.

Drug Resistance, Bacterial↗

Prevalence of erythromycin and clindamycin resistance among Streptococcus agalactiae isolates in Germany.

The antimicrobial susceptibilities of 338 clinical Streptococcus agalactiae isolates from two geographical regions in Germany were determined by agar dilution. All isolates were susceptible to penicillin, cefotaxime and vancomycin. The overall frequencies of erythromycin and clindamycin resistance were 11% and 4.7%, respectively. Determination of resistance phenotypes among the 37 erythromycin-resistant isolates revealed constitutive and inducible MLS(B) resistance in 40.6% and 37.8% of isolates, respectively, and susceptibility to clindamycin in 21.6% of isolates. Only 14.3% of isolates with inducible MLS(B) resistance were identified as clindamycin-resistant by determination of clindamycin MICs. Pulsed-field gel electrophoresis suggested a clonal distribution pattern among the erythromycin-resistant isolates.

Anti-Bacterial Agents↗

Changes in macrolide resistance among respiratory pathogens after decreased erythromycin consumption in Taiwan.

Measures to alleviate the growing problem of macrolide resistance in Taiwan resulted in a decrease in macrolide consumption, from 0.629 defined daily doses/1000 inhabitants per day (DIDs) in 1999 to 0.301 DIDs in 2003 (a reduction of 52%). A linear relationship was observed between the decline in erythromycin consumption and the decline in erythromycin resistance in Streptococcus pyogenes (46% in 1999 vs. 17% in 2003; p < 0.001) and azithromycin resistance in Haemophilus influenzae (31% in 2000 vs. 0% in 2003; p < 0.001). However, the rate of erythromycin resistance in Streptococcus pneumoniae showed a continued increase, from 80.2% in 1999 to 92% in 2003.

Anti-Bacterial Agents↗

Effects of cholinoceptor and 5-hydroxytryptamine3 receptor antagonism on erythromycin-induced canine intestinal motility disruption and emesis.

1. Erythromycin administration is associated with gastrointestinal problems, disturbed gastrointestinal motility and emesis. This study in the dog investigates the underlying mechanisms. 2. Intestinal myoelectrical activity and the occurrence and latency of emesis were recorded in eight conscious dogs. All drugs were administered intravenously. 3. Erythromycin (7 mg kg-1) increased contractions of the proximal small intestine, and caused emesis in all fasted dogs and in 5 dogs after food. Atropine (50 mg kg-1 min-1) and hexamethonium (10 mg kg-1 h-1) partially inhibited the GI motility effects but did not significantly reduce emesis. 4. Metoclopramide at a high dose (2 mg kg-1 h-1) reduced the incidence of emesis in the presence of increased intestinal motility, but a low dose (150 micrograms kg-1 h-1) was ineffective. 5. A 5-hydroxytryptamine3 (5-HT3) receptor antagonist, MDL 72222 (1 mg kg-1), reduced emesis when given alone and combined with metoclopramide (low dose). The 5-HT4 receptor agonist BRL24924 (Renzapride, 1 mg kg-1) had no effect on emesis either alone in combination with metoclopramide. 6. In conclusion, erythromycin-induced GI motility disturbances and emesis are not causally related. Whereas the increase in intestinal smooth muscle activity is possibly cholinergically mediated, emesis occurs at least in part via a 5-hydroxytryptaminergic mechanism, but does not involve the dopamine system.

Animals↗

Impetigo contagiosa: a comparison of erythromycin and dicloxacillin therapy.

One hundred patients with impetigo were prospectively enrolled in a study to determine the current etiology and comparative therapeutic efficacy of two oral antimicrobial agents active against both group A beta-hemolytic streptococci (GABS) and Staphylococcus aureus. After obtaining a bacterial culture from a representative impetiginous lesion, the children were randomized to receive 10 days of either erythromycin (40 mg/kg/day) or dicloxacillin (25 mg/kg/day). S. aureus alone was isolated from 46 children, and in association with GABS from 25 children. GABS alone was isolated from nine patients. Of the 59 evaluable children with S. aureus isolates, 28 of 29 treated with erythromycin and 29 of 30 treated with dicloxacillin were cured or improved on follow-up examination. Thus, we conclude that erythromycin is the drug of choice for impetigo in our midwestern locale because of its high efficacy and relatively low cost.

Adolescent↗

Impetigo contagiosa III. Comparative efficacy of oral erythromycin and topical mupirocin.

Ninety-seven patients with impetigo were prospectively enrolled in a study to determine the comparative efficacy of systemic and topical antibiotic therapy. After obtaining a bacterial culture from a representative lesion, the children were randomized to receive seven days of either oral erythromycin or topical mupirocin administered three times daily. Staphylococcus aureus alone was isolated from 51% and in association with group A beta-hemolytic streptococci (GABS) from 29%; GABS alone was isolated from 4% of patients. Of 48 children who received erythromycin, 43 (90%) were clinically improved or cured, and 11 of 17 were bacteriologically cured. Of 49 children who received mupirocin, 47 (96%) were clinically improved or cured, and 10 of 14 were bacteriologically cured. At three-week follow-up, clinical cure rates and number of secondary household cases of impetigo were equivalent in both treatment groups. Mupirocin appears to be a well-tolerated, albeit expensive, alternative to erythromycin for the treatment of impetigo.

Administration, Oral↗

Unit dose erythromycin ophthalmic ointment for neonatal ocular prophylaxis.

Silver nitrate solution has been used since the 1880s for newborn prophylaxis against Neisseria gonorrhoeae ocular infections. Recommendations by the American Academy of Pediatrics and the Centers for Disease Control state that erythromycin and tetracycline ophthalmic products may serve as alternatives to silver nitrate solution. The selection of erythromycin ophthalmic ointment offers the advantage of antimicrobial activity against Chlamydia trachomatis and is not associated with the chemical conjunctivitis often seen with silver nitrate solutions. The only commercially available form of erythromycin ophthalmic ointment is a 3.5-gm tube. Repackaging the ointment into tuberculin syringes reduces the cost to the patient and provides the nurse with a more convenient method of administering the ointment to the neonate.

Drug Packaging↗

The effect of erythromycin on gastric emptying is modified by physiological changes in the blood glucose concentration.

OBJECTIVE: The aim of this study was to determine whether variations in the blood glucose concentration within the normal postprandial range affect the gastrokinetic action of erythromycin. METHODS: Six healthy male volunteers, aged 20-33 yr underwent measurements of gastric emptying on 2 separate days; blood glucose concentrations were maintained at approximately 4 mmol/L (72 mg/dl) on 1 day and at 8 mmol/L (144 mg/dl) on the other. The order of the two studies was randomized and they were separated by 4-7 days. On both days, erythromycin (3 mg/kg) was administered intravenously over 15 min immediately before consumption of 300 g minced beef labeled with 20 MBq 99mTc-sulphur colloid chicken liver and 150 ml water labeled with 67Ga-EDTA. RESULTS: Gastric emptying of solid (p < 0.05) and liquid (p < 0.0001) were slower at a blood glucose concentration of 8 mmol/L (144 mg/dl) when compared to 4 mmol/L (72 mg/dl). The slowing of gastric emptying was associated with greater retention of both solid and liquid in the proximal (p < 0.06) and distal (p < 0.01) stomach. CONCLUSIONS: After administration of erythromycin, gastric emptying and intragastric distribution of solids and liquids is influenced by physiological changes in the blood glucose concentration.

Adult↗