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PubMed1989

Clinical pharmacokinetic properties of the macrolide antibiotics. Effects of age and various pathophysiological states (Part I).

The pharmacokinetic aspects in humans of macrolide antibiotics that are currently or soon to be on the market (i.e. erythromycin, oleandomycin, spiramycin, josamycin, midecamycin, miocamycin, rosaramycin, roxithromycin and azithromycin) are reviewed. Macrolide antibiotics are basic compounds, poorly soluble in water, which are mostly absorbed in the alkaline intestinal environment. They are acid unstable, but the newer semisynthetic derivatives (i.e. roxithromycin and azithromycin) are characterised by increased stability under acidic conditions. Macrolides are highly liposoluble and consequently penetrate well into tissue, especially bronchial secretions, prostatic tissue, middle ear exudates and bone tissues, as evidenced by tissue/serum concentration ratios greater than 1. They do not penetrate well into the CSF. Macrolides undergo extensive biotransformation in the liver. With a few exceptions (e.g. miocamycin), the metabolites of these drugs are characterised by little or no antimicrobial activity. Plasma protein binding is variable from one compound to another. At therapeutic concentrations, protein-bound erythromycin accounts for 80 to 90% of the total drug present in the blood, and the fraction is 95% for roxithromycin. The lowest values of protein-bound fraction are observed for midecamycin and josamycin (about 15%), and intermediate values are reported for spiramycin and miocamycin. However, the clinical relevance of this parameter is not clearly established. Plasma half-life (t1/2) values vary for the macrolides described: erythromycin, oleandomycin, josamycin and miocamycin have a t1/2 ranging from 1 to 2 hours; spiramycin, erythromycin stearate, the mercaptosuccinate salt of propionyl erythromycin and rosaramicin have an intermediate t1/2 (about 7, 6.5, 5 and 4.5 hours, respectively); the newer semisynthetic compounds roxithromycin and azithromycin are characterised by high t1/2 values (i.e. 11 and 41 hours, respectively). Under normal conditions, the major route of elimination is the liver. Renal elimination also takes place but it contributes to total clearance only to a small degree, as evidenced by low renal clearance values. The degree of modification of macrolide pharmacokinetics by renal insufficiency or hepatic disease is usually not considered clinically relevant, and no recommendation for dose modification is necessary in these patients. The pharmacokinetics of macrolides are modified in elderly patients. Accordingly, their use must be accompanied by a closer than usual clinical monitoring of the older patient.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1975

Microbial degradation of erythromycins A and B.

Growing cultures, as well as broken and lyophilized cells of pseudomonas 56 were found to degrade erythromycin A, and lyophilized cells inactivated erythromycins A and B. The enzyme system involved in this degradation was constitutive and the enzyme level in the cells could be increased about 8-fold when oleandomycin or erythromycin B was added to the growth medium. The ability of whole or broken cells to inactivate erythromycin A was completely lost when these preparations were boiled, and the erythromycin A-inactivating activity was localized in the cell membrane fraction. The lyophilized cells did not degrade oleandomycin, methymycin, tylosin, a mixture of leucomycins, josamycin, or maridomycin III.

Anti-Bacterial Agents↗
PubMed2000

Macrolide esterase-producing Escherichia coli clinically isolated in Japan.

Current Japanese clinical practice involves the usage of large amounts of new macrolides such as clarithromycin and roxithromycin for the treatment of diffuse panbronchiolitis, Helicobacter pylori and Mycobacterium avium complex infections. In this study, the phenotypes, genotypes, and macrolide resistance mechanisms of macrolide-inactivating Escherichia coli recovered in Japan from 1996 to 1997, were investigated. The isolation rate of erythromycin A highly-resistant E. coli (MIC > or = 1,600 microg/ml) in Japan slightly increased from 0.5% in 1986 to 1.2% in 1997. In six macrolide-resistant strains, recovered from the strains collected for this study during 1996 to 1997, the inactivation of macrolide could be detected with or without added ATP in the assay system. The appearance of erythromycin A-inactivating enzyme independent of ATP was novel from Japanese isolates, and the 1H NMR spectra of oleandomycin hydrolyzed by the three ATP-independent isolates were examined. It was clearly shown that the lactone ring at the position of C-13 was cleaved as 13-H signal in aglycon of oleandomycin upper shifted. These results suggested the first detection of macrolide-lactone ring-hydrolase from clinical isolates in Japan. These results suggested the first detection of an ATP-independent macrolide-hydrolyzing enzyme from Japanese clinical isolates. Substrate specificity of the macrolide-hydrolyzing enzyme was determined with twelve macrolides including the newer members of this group and it was found that not only erythromycin A but also the new macrolides, such as clarithromycin, roxithromycin, and azithromycin were inactivated. The NMR data, broad spectrum of activity, and independence of co-enzyme supported our naming of the enzyme as a macrolide esterase. PCR methodology was employed to detect an ereB-like gene from the 3 isolates producing macrolide esterase, and one of these was subsequently shown to contain both ereB-like and ermB-like genes. It was also clearly shown that the other three isolates, which inactivated macrolide in the presence of ATP, had an mphA-like gene.

Anti-Bacterial Agents↗
PubMed1999

Appearance in Japan of highly macrolide-resistant Escherichia coli producing macrolide 2'-phosphotransferase II.

Escherichia coli CU1, a clinical isolate recovered in Japan in 1997, was found to be highly-resistant to both 14-membered and 16-membered ring macrolide antibiotics. A crude extract prepared from strain CU1 inactivated 14-, 15- and 16-membered ring macrolides in the presence of ATP and the Rf value of inactivated oleandomycin was identical to that of oleandomycin 2'-phosphate. This suggested that strain CU1 produced the enzyme macrolide 2'-phosphotransferase [MPH(2')]. Substrate specificity of the crude enzyme from strain CU1 against 14-, 15- and 16-membered ring macrolides was basically similar to that of MPH(2')II from strain BM2506, differing in that the former more effectively inactivated roxithromycin and tylosin. Subsequent attempts were made to clone the novel mph gene encoding for MPH(2') in strain CU1. The mph gene carried by strain CU1 was located on nontransmissible plasmid DNA, designated pCU001. Its molecular weight, estimated by agarose electrophoresis, was approximately 57 kD. The DNA sequence of the cloned mph gene from the Japanese isolate CU1 was identical to that of mphB, which until now had only been recovered in France. The variance in the substrate specificity of MPH(2')II from each strain led us to speculate that other factors in the reaction affect the enzymatic inactivation activity.

Anti-Bacterial Agents↗
PubMed2001

[Susceptibility to macrolide antibiotics of Bordetella pertussis and Bordetella parapertussis strains isolated from whooping cough patients in 1968 and in 1997-99].

The activity of erythromycin, azithromycin, clarithromycin, dirithromycin, oleandomycin, roxithromycin, spiramycin and josamycin against 21 and 34 B. pertussis strains and against 6 and 8 B. parapertussis strains isolated respectively in the years 1968 and 1997-99 was examined. The antibiotic agar dilution method was used. The minimum concentration of macrolides which inhibited growth of B. pertussis and B. parapertussis was calculated for 50% (MIC50) and 90% (MIC90) of isolates. The susceptibility to macrolides of B. pertussis and B. parapertussis strains isolated in the years 1968 and 1997-99 did not differ significantly. The MIC90 values of erythromycin were the same for B. pertussis (MIC90 = 0.125 mg/l) and B. parapertussis strains (MIC90 = 0.25 mg/l) recovered in 1968 as for those recovered in the years 1997-99. The most active antibiotic against all strains was azithromycin (MIC90 = 0.06 mg/l). The least active antibiotics were oleandomycin (MIC90 = 2-4 mg/l) and spiramycin (MIC90 = 8 mg/l). The study showed that erythromycin remains the antibiotic of choice for treatment of whooping cough and in case of emergence of B. pertussis and/or B. parapertussis strains erythromycin resistant, can be replaced by azithromycin.

Anti-Bacterial Agents↗
PubMed1978

[Geographical race typing of the causative agent of tularemia using antibiotics].

Reaction of the strains of the tularemia causative agent to erythromycin (100 gamma/ml) or oleandomycin (400 gamma/ml) is one of the taxonomic tests. The study of 82 strains of the holarctic race and 63 strains of the Central Asiatic race according to this test showed that the strains of the holarctic race were divided with respect to these macrolides into sensitive (biotype I) and resistant (biotype II). The strains of the both races were isolated at the territory of the Kazakh SSR. Such a reaction of the strains of the holarctic race is a stable feature and is not connected with virulence, the isolation source and the biochemical properties of the strains. Division of the holarctic race into the biotypes (I and II) with respect to erythromycin and oleandomycin may be of definite significance in epidemiological and epizootological examination for tularemia with a purpose of determining the source of the infection, as well as in defining the borders of the infection focus area with circulation of this or that biotype of the holarctic race of the tularemia causative agent.

Anti-Bacterial Agents↗
PubMed1979

[Staphylococcus aureus in poultry--biochemical characteristics, antibiotic resistance and phage pattern (author's transl)].

In a poultry processing plant in northern Germany 1412 swabs were taken from poultry carcasses together with 608 swabs from the personnel. The broilers came from 22 different chicken farms. The swabs taken from the poultry and those taken from the personnel proved to be 35% and 48% Staph. aureus positive respectively. The swabs taken from the feathers and from the skin were staphylococcal positive at a higher level (47%) than the swabs taken from the cloaca (19%) and the throat (23%). Between 8% and 63% of the animals from the various chicken farms were Staph. aureus positive. The frequency of staphylococcal contamination increased during the course of slaughter. 57% of the swabs taken from the gloves and the hands and 42% from the aprons of the personnel were Staph. aureus positive. Some biochemical properties, the phage patterns, and the antibiotic resistance against oleandomycin, erythromycin, bacitracin, streptomycin, tetracyclin, penicillin, chloramphenicol, virginiamycin and flavomycin were determined from 445 poultry and 345 personnel Staph. aureus isolates. Only small differences could be established between both sources in this way. Only 20% of the personnel and 34% of the chicken strains were resistant to antibiotics. In the strains collected from personnel, penicillin-resistance predominated while the poultry isolates showed predominantly tetracyclin-resistance. Of all antibiotics applied nutritively in the chicken fattening, there was a higher resistance only against oleandomycin (11% of the poultry strains). Between the chicken farms there was a different frequency of resistance (0--68%). The source of the staphylococci could be determined for only some of the strains. Only 2.5% of the chicken isolates showed characteristics described in the literature to be "poultry-specific", whereas 37% of the personnel and 24% of the poultry isolates were shown to be "human-specific" strains. It seems that the vast majority of the staphylococci originated from the slaughterhouse personnel. The rest of the strains differed in varying combinations of their properties from the given species characteristics. Although Staph. aureus was brought into the slaughterhouse by the poultry, the contaminations of the final product seemed to originate mainly from human beings.

Abattoirs↗
PubMed1977

[Antibiotic sensitivity of the bacterial microflora from the sputum of children with acute pneumonia].

Bacteriological analysis of sputum of 598 children with acute pneumonia was performed. Sensivity of 1348 cultures belonging to 8 bacterial species with respect to benzylpenicillin, streptomycin, chloramphenicol, tetracycline, oxytetracycline, chlortetracycline, erythromycin, oleandomycin, neomycin and monomycin was determined. It was shown that the sputum microflora was often resistant to the antibiotics widely used in the medical practice for prolonged periods of time, such as benzylpenicillin, streptomycin, chloramphenicol, tetracyclines. However, it usually remained sunsitive to neomycin, monomycin, erythromycin and oleandomycin. It was found that antibioticogrammes defining the antibiotic choice were of great significance for therapy of acute pneumonia.

Acute Disease↗
PubMed1990

[Comparative analysis of antibiotic sensitivity of Streptococcus pneumoniae strains isolated from patients and carriers].

The data on antibiotic sensitivity of 38 strains of S. pneumoniae isolated from children and 46 strains isolated from carriers are presented. The isolates from the carriers had significantly higher sensitivity to benzylpenicillin, ampicillin, methicillin, oxacillin, cefazolin, erythromycin, oleandomycin and lincomycin. Resistance to gentamicin was more frequent in the strains isolated from the carriers. Among the strains of S. pneumoniae isolated from the patients and carriers representatives of serovar K19 were more frequent. There were no statistically reliable difference in them by sensitivity to benzylpenicillin, ampicillin, cefazolin, lincomycin and rifampicin. Still, the isolates from the carriers were much more sensitive to methicillin, oxacillin, oleandomycin and erythromycin.

Anti-Bacterial Agents↗
PubMed1978

[Effect of hydroacridine derivatives on the sensitivity of polyresistant strains of Staphylococcus aureus and Escherichia coli to antibiotics].

Sensitivity of 4 clinical strains of Staph. aureus and E. coli to 13 hydroacridine derivatives and their combinations with antibiotics, such as benzylpenicillin, ampicillin, semi-synthetic penicillins, streptomycin, chloramphenicol, tetracycline, chlortetracycline, monomycin, oleandomycin and erythromycin was studied. The highest bacteriostatic effect was observed on the use of perhydroactidine derivatives with benzylpenicillin or ampicillin with respect to polyresistant penicillinase-producing strains of Staph. aureus, resistance of which to these antibiotics was decreased 250--1000 times. Under the effect of the above compounds the staphylococcal resistance to chloramphenicol, tetracycline, chlortetracycline, oleandomycine and erythromycin decreased 2--66 times. The combinations of hydroacridine with the antibiotics, except 10-amino-trans-syn-trans-perhydroacridine had no effect on the resistance of the E. coli strains. The results of the combined effect of the above substances were associated with their chemical nature, the bacterial type and possibly the character of the strain resistance.

Acridines↗
PubMed1978

[Experimental study of the antimicrobial effect of lysozyme in combination with antibiotics].

A synergistic effect of the antibacterial action of the lysozyme combination with various antibiotics against gram-positive and gram-negative microorganisms was found. The intensifying effect of lysozyme on its combination with antibiotics was more evident with respect to gram-positive microbes and less evident with respect to gram-negative organisms. The combinations os lysozyme with methicillin, lincomycin, oleandomycin or erythromycin proved to be most active against staphylococci. A high synergistic effect against streptococci was observed with the use of the lysozyme combination with benzylpenicillin, morphocycline, oleandomycin, ceporin or monomycin. The combination of lysozyme with macrolides had a maximum inhibitory effect on Coli bacteria.

Anti-Bacterial Agents↗
PubMed1977

[Sensitivity of Sherman's propionic acid bacilli to antibacterial preparations and vitamin B12 synthesis].

Sherman propionic acid bacilli were sensitive to benzylpenicillin, ampicillin, ceporin, tetracyclines, oleandomycin, oletetrin, tetraolean, sigmamycin, levomycetin and furadonine. Methicillin, oxacillin, monomycin, kanamycin, polymyxin and furazolidone had an insignificant effect on the above organism. The subbacteriostatic concentrations of methicillin, oxacillin, streptomycin, monomycin, kanamycin, neomycin, tetraolean, sigmamycin, polymyxin M and ristomycin increased the biosynthesis of vitamin B12 by Sherman propionic acid bacilli, while benzylpenicillin, ampicillin, tetracyclines, oleandomycin, oletetrin, levomycetin and furadonine in the subbacteriostatic concentrations inhibited this process.

Anti-Bacterial Agents↗
PubMed1984

[Interrelation of the antibiotic sensitivity (resistance) of staphylococci, clinical forms of the infection and production of protein A].

Two hundred and thirty-two strains of Staph. aureus isolated from patients with staphylococcal infections were studied. The strains were isolated from the blood of patients with sepsis, from the purulent foci on the skin and in the subcutaneous fat, from the nasopharyngeal mucosa of patients with tonsillitis and inflammation of the upper respiratory tract, from the sputum of patients with the pneumonia signs and from the pus of patients with otitis. The pathogens were identified with the routine methods. The quantitative content of protein A in the strains was determined by the method of indirect hemagglutination with red blood cells sensitized with the hemolytic serum. The data obtained were analysed with regard to the strain group and characteristics of the strain resistance or sensitivity to benzylpenicillin, erythromycin, oleandomycin, chloramphenicol, streptomycin, neomycin, kanamycin, monomycin, ristomycin and furagin K. Statistically significant differences in the protein A content in certain strain groups were observed. These differences might be correlated with the strain antibiotic resistance but not sensitivity. Pronounced changes in the levels of protein A were detected in the staphylococcal hemocultures resistant to erythromycin and streptomycin. The cultures resistant to erythromycin were characterized by decreased content of protein A and those resistant to streptomycin were characterized by increased content of protein A. Comparison of the antibiotic sensitivity of the strains of 5 groups by variation statistics revealed significant differences in the levels of sensitivity to streptomycin, neomycin, kanamycin, monomycin, ristomycin and furagin K but not to erythromycin, oleandomycin and chloramphenicol in the strains of certain groups. The staphylococcal hemocultures isolated from patients with sepsis proved to be the most sensitive to the antibiotics.

Adult↗
PubMed1978

[Sensitivity of the causative agent of tularemia to antibiotics].

Sensitivity of the tularemia causative agent of different geographical races to antibiotics such as streptomycin, tetracycline, gentamicin, rifampicin (20 strains), ampicillin, polymyxin M, erythromycin, oleandomycin (361 strains) and lincomycin (294 strains) was studied. High sensitivity of the tularemi a microbe to streptomycin, tetracycline, rifampicin (MIC of 10 gamma/ml), gentamicin (MIC of 1 gamma/ml) and resistance to 50 gamma of ampicillin and 1000 gamma/ml of polymyxin M were found. Combined use of 50 gamma of ampicillin and 100 gamma/ml of polymyxin M added to the nutrient medium for growth inhibition of the foreign flora on isolation of the tularemia causative agent from the infected material including stable laboratory animal carcases was recommended. Marked differences in sensitivity of the strains of different geographical races to the macrolides and lincomycin were observed. The strains of the non-Arctic and Central Asiatic races were of low resistance to the above drugs (the MIC of erythromycin, oleandomycin and lincomycin were 10--50, 50--400 and 25--100 gamma/ml respectively. Within the holarctic race 40 per cent were low resistant and 60 per cent were highly resistant to these drugs. The above drugs should not be used for treatment of tularemia cases.

Anti-Bacterial Agents↗
PubMed1981

[Comparative antibiotic sensitivity characteristics of the staphylococci isolated from ambulatory and hospitalized patients].

Sensitivity of staphylococci isolated from the pathological material of outpatients with purulent inflammatory infections and inpatients was studied with respect to 10 antibiotics. The agar diffusion method with standard paper discs impregnated with the antibiotics was used. It was shown that the majority of the staphylococcal cultures isolated from the outpatients was sensitive to the aminoglycoside antibiotics: neomycin 89.7 per cent, monomycin 87.3 per cent and kanamycin 82.9 per cent. The sensitivity of the isolates to benzylpenicillin, levomycetin, erythromycin and oleandomycin was lower and amounted to 63.5, 64.6, 66 and 69 per cent respectively. The sensitivity of the cultures isolated from the inpatients to benzylpenicillin, erythromycin, oleandomycin and levomycetin amounted to 43.4, 45.5, and 49.5 and 53.3 per cent respectively. The comparative study on the antibiotic resistance pattern showed that more than a half of the cultures isolated from the inpatients were polyresistant (resistance to 4--10 antibiotics). The number of such cultures isolated from the outpatients amounted to 32.8 per cent. Cultures sensitive to all of the antibiotics tested and resistant to 1, 2 or 3 of them predominated in this group of the isolates.

Ambulatory Care↗
PubMed1976

[Sensitivity of 30 strains of E. coli isolated from calves to chemotherapeutic agents].

Escherichia coli strains were isolated from calves and were biochemically and serologically identified in terms of their sensitivity to antibiotics. An exclusively high frequency of sensitivity was established to sulfonamides (100 per cent), tetracicline, erythromycin, oleandomycin (86.6 per cent) ampicillin, and streptomycin (70 per cent). Well expressed was their sensitivity to nitrofurans, canamycin, neomycin, and polymyxin. It was demonstrated through serial dilutions that there exists a high level of resistance to sulfanilamides, oleandomycin, erytromycin, tetracycline, streptomycin, chloramphenicol (more than 512 mug/cm3). The prevalence of such polyresistand E. coli strains in calves is the reason for concern in the district of Haskovo.

Animals↗
PubMed1976

[Biochemical identification of Salmonella and coli bacteria and their sensitivity to chemotherapeutic agents].

Strains of enterobacteria, isolated from pathologic material (dead pigs, birds, lambs, sheep fetuses, swab fecal samples from calves) were biochemically identified by the methods of Costin, Le Minor, and Eming. One-hundred forty of them proved to belong to Escherichia coli and 236 -- to Salmonella. The sensitivity of the isolated bacteria to antibiotics (ampicillin, streptomycin, tetracyclin, kanamycin, neomycin, chloramphenicol, erythromycin, oleandomycin polymyscin), sulfonamides (norsulfasol, sulfaguanidine, and sulfadimesine), and nitrofuran preparations (furazolidon and orafuran) was tested by the disk diffusion method. There was in a high per cent of the cases resistance to tetracyclin, erytromycin, oleandomycin, sulfanilamides, streptomycin, ampicillin, and comparatively well expressed susceptibility to polymyxin, furazolidon, orafuran, kanamycin, neomycin and chloramphenicol. Prevailing were the enterobacteria polyresistant to antibiotics, the observed resistance being expressed to 3, 4, 5, 6, and 7 antibiotics at the same time (out of all nine of them that were studied). The only exception were Salmonella typhimurium and Salmonella dublin which were resistant to 2 or 3 antibiotics only. In connection with the data obtained on the tolerance of enterobacteria to chemotherapeutics it is necessary to reevaluate the programmes for the prophylaxis and control of diseases in farm animals and birds caused by Escherichia coli Salmonella spp.

Animals↗
PubMed1998

[Resistance to macrolide antibiotics found in methicillin-resistant Japanese clinical isolates of Staphylococcus aureus in 1996].

Minimum inhibitory concentrations (MICs) of erythromycin, clarithromycin, roxithromycin, oleandomycin, triacetyloleandomycin, azithromycin, josamycin and midecamycin were investigated using 200 strains of methicillin-resistant Staphylococcus aureus (MRSA) clinically isolated in Japan during 1996. The results show that the MRSAs could be classified into five groups according to MIC patterns to various macrolides and that more than 88% of the strains used were highly-resistant to all macrolides tested. It was found that 9.0% of the strains examined showed a unique MIC pattern different to that of macrolide-lincosamide-streptogramin B antibiotic resistance type. This group was found to be highly resistant to 14-membered but susceptible to 16-membered macrolides. The resistance induction by erythromycin or oleandomycin was observed to increase for clarithromycin and roxithromycin resistances in a part of strains used. On the other hand, for azithromycin, such induction was not observed.

Anti-Bacterial Agents↗