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24 patients suffering from papulo-pustular acne were treated with mono-therapy with 2% erythromycin-containing alcoholic solution for eight weeks. Pustular lesions responded promptly, followed by inflammatory papules. Microbiological investigations revealed a lack of propionibacteria as well as reduction of pathogenic staphylococci. Patients after extended local erythromycin treatment did not show any erythromycin serum levels.
Ten institutions participated in a controlled clinical trial in order to evaluate the efficacy of topical meclocycline and erythromycin in comparison to placebo with regard to papulopustular acne. Both drugs had been incorporated in the same galenic formulation that served as placebo. The vehicle employed in this study guaranteed equally favorable drug relies for both preparations. At the end of the trial, 419 patients could be evaluated for efficacy. As impartial criterion for evaluation, the number of inflammatory lesions on the right side of the face was counted before and after three months of treatment. In addition, we recorded the patients' and physicians' overall judgment at the end of the study. As compared with placebo, meclocycline as well as erythromycin brought about statistically significant improvement already after two months of treatment. After three months, the results were statistically very highly significant (p less than 0.001). At any time of the study, there could not be demonstrated any difference between the two groups treated with meclocycline and erythromycin.
Rabbits were immunized with suspensions of Streptococcus pyogenes grown, either in the presence of subinhibitory concentrations of erythromycin (1/2 and 1/8 MIC) or without antibiotic. Over a twelve-week period, the opsonic activity of the serum and the levels of various streptococcal antibodies were determined. For the two test strains, the immune response observed was identical for the vaccine grown with 1/8 MIC erythromycin and for the control vaccine. The vaccines grown with 1/2 MIC of erythromycin induced a slower and weaker elaboration of protective antibodies.
The effects of a 1.5 percent solution of erythromycin, especially formulated for the topical treatment of acne vulgaris, were compared with those of its vehicle in a twelve week, double-blind study involving twenty-six patients. A statistically significant difference between the responses to the two treatments was seen in both lesion counts and overall evaluations. The final reductions in the mean number of papules and pustules in the erythromycin group were 70.8 and 77.6 percent of the initial values, respectively, and the overall evaluations of this group showed that 91.7 percent of the patients had achieved good or excellent results. A group of fourteen patients continued therapy with the erythromycin solution for an additional nine months. Effective control of their acne was maintained, and no serious side effects were observed.
Current recommendations for antibiotic prophylaxis of bacterial endocarditis include oral amoxycillin, and erythromycin or clindamycin for the penicillin-allergic patient. The authors report the serum concentrations and side effects which may be expected after the recommended oral doses of these compounds. Single doses of 3 g amoxycillin and 600 mg clindamycin, and two doses of erythromycin (1.5 g and 0.5 g 6 h apart) were administered in a random sequence to each of 12 volunteers. After administration, peak serum concentrations of amoxycillin and clindamycin were 27 mg/l and 5.5 mg/l respectively. Amoxycillin was eliminated more rapidly than clindamycin. Serum concentrations of erythromycin were below the sensitivity limit of the assay (0.03 mg/l) in 3 volunteers at 1 h and in 2 at 2 h. The mean peak serum concentrations was 3.1 mg/l. Peak levels were associated with gastrointestinal side effects such as nausea, abdominal cramps and vomiting. The implications of these findings are discussed with respect to use of these antibiotics for the prophylaxis of bacterial endocarditis.
Twenty-six patients aged between 27 and 71 years with chronic bronchitis were divided into a control group of 6 and two groups of 10 patients each who received either erythromycin stearate or amoxycillin 1500 mg/d for 2 weeks and 1000 mg/d for 12 weeks thereafter. Immunological function tests were performed before starting chemotherapy and thereafter at 2 weeks and 14 weeks. Clinical evaluations and lung function tests showed no significant changes in any of the groups during the study period. In the control group no changes in cellular and humoral immune functions were noted. In the group receiving amoxycillin decreased responses of lymphocytes to the mitogen phytohaemagglutinin were observed after 14 days. In the erythromycin-treated group, increased polymorphonuclear leucocyte (PMNL) motility and mitogen-induced transformation were observed at 14 days but these increases were not statistically significant. In this group the markedly depressed PMNL migration found in 3 individuals before treatment improved considerably. These results indicate that chemotherapy and chemoprophylaxis with either amoxycillin or erythromycin stearate do not compromise the host immunodefences.
The tetracyclines are active in vitro against many urinary tract pathogens such as Chlamydia, Mycoplasma pneumoniae, Brucella, rickettsiae, and Nocardia. Chloramphenicol is used primarily for anaerobic infections, Haemophilus influenzae meningitis, and infections due to Salmonella typhi. Erythromycin is active in vitro against M. pneumoniae, Legionella spp., Streptococcus pneumoniae, and group A beta-hemolytic streptococci; it may also be used as prophylactic therapy for subacute bacterial endocarditis and for recurrence of acute rheumatic fever in patients who are allergic to penicillin. Clindamycin should be used primarily for the treatment of anaerobic infections. The tetracyclines may cause gastrointestinal upset; phototoxic dermatitis; hepatitis, especially in pregnant women; discoloration of the teeth and bone dysplasia in the human fetus and in children; and superinfections, especially oral and anogenital candidiasis. The tetracyclines should be used with caution in patients with renal insufficiency. The most important toxic effect of chloramphenicol is bone marrow suppression, which is dose related or idiosyncratic. The incidence of undesirable side effects associated with the use of erythromycin is low; gastrointestinal irritation is the most common, and cholestatic hepatitis may occur with the use of erythromycin estolate. Pseudomembranous colitis is the most important toxic effect associated with the use of clindamycin.
A left upper lobe pneumonia developed in a patient who was receiving hemodialysis; he was treated intravenously with 1 g of erythromycin lactobionate every six hours. After five doses, hearing loss was noted; this was later documented by audiogram. Erythromycin serum concentrations as high as 100 mg/L and a half-life more than three times longer than normal were observed. To our knowledge, this represents the first report of reversible hearing loss associated with elevated serum erythromycin concentrations and prolonged serum half-life.
Bioavailability of erythromycin and colistin was studied in plasma, ruminal liquid and nasal mucus after simultaneous injection by intraruminal or intramuscular route. After intramuscular injection, erythromycin was found in plasma and respiratory tract, colistin in plasma. After oral administration, only erythromycin was found in nasal cavity secretions but nitrogen metabolism and volatile fatty acid production were modified in rumen.
Sixteen adult male patients (aged between 20-38 years) with ear, nose and throat infections, caused by bacteria sensitive to erythromycin, received daily infusions of 2 x 1 g erythromycin for 48 hours. The duration of infusion was 30 or 60 minutes, administered at intervals of 12 hours between infusions. Symptoms of intolerance such as nausea, retching, feeling of pressure in epigastric angle as well as abdominal cramps occurred as side-effects in many cases. A spasmolytic was given intravenously to twelve patients; it rapidly eliminated the symptoms. However, these side-effects were considered insignificant compared to the excellent clinical results obtained during infusion therapy. We, therefore, believe that 2 x 1 g/day erythromycin per infusion can be regarded as the drug of choice in chronic and acute ear, nose and throat infections. The rapid resolution of infections, which are otherwise difficult to treat, and the concomitant decrease in confinement to bed by about 8 to 10 days are the most important results in this study.
Correlations between the bioavailability parameters for erythromycin stearate tablets from five manufacturers and in vitro tests of these tablets were examined using forward (stepwise), multiple linear regression analysis. Bioavailability parameters were determined in clinical studies employing a balanced, incomplete block design. In vitro tests used disintegration, dissolution, and dissolution/dialysis as the independent variables in regression equations. Significant correlations were found between linear combinations of these parameters and the time of peak and the peak serum levels. The inclusion of an in vitro disintegration test to describe peak serum levels of erythromycin is noteworthy since it has been suggested that disintegration tests are of less value than dissolution techniques employed in the present investigation may be useful for selection of appropriate physicochemical tests for continued monitoring of the bioavailability of erythromycin stearate tablets.
Erythromycin is a widely used antibiotic in today's armamentarium of antibiotics. Although erythromycin induced ventricular tachyarrhythmia is rare, this potentially life-threatening reaction should be kept in mind. The relative rarity of 'torsades de pointes' arrhythmia suggests that other predisposing factors contribute to the acquired long QT syndrome. Since more and more macrolide products have been approved by the Food and Drug Administration for use in the United States, the potential problem with 'torsades de pointes' may exist with each of the macrolide antibiotic. Until the exact mechanisms of the arrhythmia are worked out, close monitoring of rhythms and QT intervals of high risk patients who require erythromycin is certainly advisable. Only a heightened awareness among the physicians and medical personnel can the adverse outcome be minimized.
Fifteen patients with non-insulin dependent diabetes mellitus (NIDDM) were included in the study. Esophageal motility, including esophageal mean transit time (MTT), residual fraction (RF), and retrograde index (RI), was evaluated and calculated by the radionuclide esophageal transit test (RETT). The baseline study was performed before the oral erythromycin therapy. After a 2-week course treatment, the subjects underwent a second study. The results showed that (A) in the baseline study, 93% (14/15) of NIDDM patients had a longer MTT, 67% (10/15) had a higher RF and 80% (12/15) had a higher RI; and (B) after treatment with erythromycin, 73% (11/15) of the patients had a shorter MTT and a lower RF, and 60% (9/15) of the patients had a lower RI. We conclude that (1) most of the NIDDM patients had esophageal motility disorders and (2) a 2-week oral erythromycin therapy can improve diabetic esophagoparesis, as evaluated by non-invasive REET.
The study of the antibacterial activity of ditetracycline combination with erythromycin (ratio 1 : 1) showed that the effect of the antibiotics increased with respect to most of Staphylococcus and Coli bacteria. The chemotherapeutic effect of the ointment in treatment of experimental staphylococcal conjunctivitis of rabbits was also studied. The clinical signs of the disease disappeared earlier than in the experiments with the use of ditetracycline and erythromycin ointments alone. The experiments with the rabbits revealed a prolonged effect of the ointment: ditetracycline and erythromycin in therapeutic concentrations were detected in the conjunctiva and cornea after a single application for 24--48 and 8 hours respectively.
The CYP3A subfamily of cytochromes P450 metabolize many medications and environmental contaminants. CYP3A4 and, in 25% of patients, CYP3A5 seem to be the major CYP3A genes expressed in adult liver. Hepatic levels of CYP3A4 can be estimated by the erythromycin breath test and vary at least 10-fold among patients. CYP3A4 has also been shown to be present in small bowel where it is responsible for significant "first-pass" metabolism of orally administered substrates. However, it is not known whether there is significant interindividual variability in the intestinal expression of CYP3A4, or whether the liver and intestinal catalytic activities of CYP3A4 correlate within an individual. It is also not known whether CYP3A5 is expressed in the small intestine. To address these questions, we administered the erythromycin breath test to 20 patients and obtained biopsies from their small bowel. There was a 6-fold variation in CYP3A catalytic activity (midazolam hydroxylation), an 11-fold variation in CYP3A4 protein content, and an 8-fold variation in CYP3A4 mRNA content in intestinal biopsies. There was an excellent correlation between intestinal CYP3A4 protein level and catalytic activity (r = 0.86; p = 0.0001); however, neither parameter significantly correlated with hepatic CYP3A4 activity as measured by the erythromycin breath test result (r = 0.27; p = 0.24 and r = 0.33; p = 0.15, respectively). We also found that CYP3A5 protein was readily detectable in biopsies from 14 (70%) of the patients, indicating that CYP3A5 is commonly expressed in human small intestine.(ABSTRACT TRUNCATED AT 250 WORDS)
In 1993, a total of 6586 cases of pertussis was reported in the United States, including 70 in Arizona. On June 27, 1994, a case of Bordetella pertussis disease caused by a strain resistant to erythromycin was reported to the Arizona Department of Health Services (ADHS) from Yuma County (1990 population: 106,895). Susceptibility testing at CDC confirmed that the isolate was highly resistant to erythromycin with a minimum inhibitory concentration (MIC) > 64 micrograms/mL. The MIC of erythromycin against B. pertussis usually ranges from 0.02 micrograms/mL to 0.1 micrograms/mL, and resistant isolates have not been previously reported (1). This report summarizes the case investigation and describes efforts to enhance surveillance for pertussis in Arizona.
To elucidate whether macrolide antibiotics affect cholinergic neuro-effector transmission in the airway, we studied canine isolated bronchial segments under isometric conditions in vitro. Addition of erythromycin (3 x 10(-4) M) attenuated the contractile responses to electrical field stimulation (EFS), so that the stimulus frequency required to produce a half-maximal contraction (ES50) increased from 1.3 +/- 0.3 to 5.1 +/- 0.5 Hz (p < 0.001). This effect was concentration-dependent and not influenced by propranolol, indomethacin, ouabain or mechanical removal of the epithelium. In contrast, contractile responses to acetylcholine were not altered by erythromycin. These results suggest that erythromycin may inhibit neuro-effector transmission in the airway cholinergic motor pathway, probably involving the reduction of exocytotic release of acetylcholine from the nerve terminals.
The absence of pyruvate and insignificant levels of alpha-keto-glutarate in the mycelium during the fermentation cycle were characteristic of a highly active erythromycin-producing strain of Saccharopolyspora erythraea. Alpha-keto-glutarate partially excreted to the fermentoffon broth. The activity of pyruvate decarboxylase and alpha-keto-glutarate decarboxylase was detected in the cells during the entire period of the cultivation. The same regularities were observed in the chloramphenicol resistant mutant of the strain. The mycelium of a low productive strain of S.erythraea contained not only alpha-keto-glutarate but also pyruvate and excreted large amounts of keto-acids. By the activity levels of the decarboxylases the low productive strain did not differ from the highly productive one. Propanol did not influence the growth of the low productive strain and the synthesis of erythromycin by it. However, it stimulated accumulation of keto-acids and especially pyruvate in both the mycelium and fermentation broth. Relation between the intensity of keto-acid metabolism and erythromycin biosynthesis is discussed.