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[Erythromycin and ciprofloxacin resistant Campylobacter jejuni].

BACKGROUND: Diarrhoea caused by Campylobacter is normally a self-limiting disease, but treatment with antibiotics may be indicated in very severe or complicated cases or in immunocompromised patients. This makes knowledge of the susceptibility of the Campylobacter to antibiotics important. MATERIAL AND METHODS: We examined retrospectively the in vitro susceptibility to erythromycin and ciprofloxacin of 296 C. jejuni strains isolated during the 1998-99 period. Particular attention was paid to the area in which the infection was acquired. RESULTS: Ciprofloxacin-resistant isolates were found in 69 (23%) of the patients. Among 121 patients probably infected abroad, the rate of resistance was 46%, highest among patients infected in Southern Europe (59%), followed by Asian and African countries. Such resistance was not recorded among strains acquired in Norway. Only one isolate showed resistance to erythromycin. A few strains showed intermediate susceptibility to both antibiotics. INTERPRETATION: During the 1998-99 period, nearly one in four of all C. jejuni isolates in Sør-Trøndelag County, Norway, were resistant to ciprofloxacin. Resistant isolates were acquired outside Norway. Resistance of C. jejuni to erythromycin occurred very rarely. In Norway erythromycin should still be the drug of choice in campylobacteriosis in cases where antibiotic treatment is indicated.

Anti-Bacterial Agents↗

[Susceptibility to penicillin and 13 antimicrobial agents in erythromycin-resistant viridans group streptococci isolated from blood cultures].

From March 1998 to June 1999, we studied 63 sequential blood culture isolates of viridans group streptococci which showed a 49% resistance to erythromycin. A high level of resistance to penicillin (46%) was also found. A statistically significant correlation was detected between the two types of resistance. The erythromycin-resistant strains were phenotypically and genotypically characterized, and no differences were found between the resistance to penicillin and the M or MLS(B) phenotypes. The penicillin-erythromycin-resistant strains included: 16 S. mitis, five S. sanguis and one S. salivarius. The rank order of activity (% of susceptibility) for all 14 agents against 31 erythromycin- resistant isolates was the following: vancomycin = rifampicin (100) > chloramphenicol (98) > meropenem (65) > cefotaxime (61) > amoxicillin- clavulanic acid (42) > cefepime = ciprofloxacin (39) > tetracycline = trimethoprim-sulfamethoxazole (36) > cefuroxime (32) > penicillin = ampicillin = cefaclor (29). The species S. milleri and S. bovis were the most susceptible. The most resistant strains were two S. mitis and one S. sanguis and showed multiresistance to six different groups of antimicrobial agents. The frequent association between macrolide resistance and resistance to other antimicrobial agents suggests that the susceptibility of all clinically significant isolates needs to be evaluated and alternative agents for the prevention and treatment of viridans group streptococci infections should be identified.

Drug Resistance↗

[Effects of erythromycin and fosfomycin on Pseudomonas aeruginosa biofilm in vitro].

OBJECTIVE: To observe the effects on Pseudomonas aeruginosa biofilm of non-antipseudomonal drugs such as erythromycin and fosfomycin. METHODS: Clinical isolates of Pseudomonas aeruginosa in respiratory infection and ATCC27853 were cultivated in TSB-Teflon and NS-Teflon system respectively for biolfilm formation. Biofilm was observed under scanning electronic microscope (SEM). MICs were determined by broth micro-dilution. RESULTS: SEM showed that biofilm of clinical isolate in TSB-Teflon system and ATCC27853 in NS-Teflon system increased as being cultivated for longer in 1, 3 and 7 days. And biofilm formation in the process of cultivating was inhibited by SubMIC of erythromycin and fosfomycin. MICs evaluation suggested that there were synergetic effects against biofilm Pseudomonas aeruginosa when SubMIC of erythromycin and fosfomycin were combined with ceftazidime or levofloxacin in vitro. CONCLUSION: SubMIC of erythromycin and fosfomycin could inhibit Pseudomonas aeruginosa biofilm in vitro.

Anti-Bacterial Agents↗

[In vitro activity of six fluoroquinolones and penicillin against 101 viridans group streptococci characterized by their susceptibility to erythromycin].

The increase in the use of the fluoroquinolones, including for the treatment of lower respiratory tract infections, seems to be associated with a parallel increase in bacterial resistance. We studied the activity of penicillin and six fluoroquinolones against 101 viridans group streptococci isolated from blood (58 erythromycin-susceptible and 43 erythromycin-resistant). The percentage of strains not susceptible to penicillin was 35% and there were statistically significant differences in the percentages of penicillin resistance between erythromycin-susceptible and -resistant strains. The fluoroquinolones studied showed good activity against our viridans group streptococci independent of their susceptibility to erythromycin. The norfloxacin MIC(50) and MIC(90) were 8 and 16 mg/l, respectively. Ofloxacin and ciprofloxacin showed the same activity (MIC(50) 1 mg/l and MIC(90) 2 mg/l); levofloxacin was similar with MIC(50) and MIC(90) of 1 mg/l. The fluoroquinolones with enhanced activity were moxifloxacin and trovafloxacin (MIC(50) 0.12 mg/l and MIC(90) 0.25 mg/l). However, we found two strains resistant to trovafloxacin (MIC = 4 mg/l) that showed reduced susceptibility to all the fluoroquinolones tested, including moxifloxacin (MIC = 2 mg/l). Mutations in the topoisomerase genes parC and gyrA have been shown to occur in strains with reduced susceptibility; therefore, ongoing surveillance for the development of fluoroquinolone resistance in viridans streptococci is necessary.

Anti-Infective Agents↗

Comparison of effects of cholecystokinin and erythromycin on bile chemistry and gallstone formation in aged guinea pigs.

BACKGROUND: There has been considerable interest in gall bladder motility in recent years. We compared the effects of cholecystokinin (CCK) and erythromycin on bile chemistry and gallstone formation in aged guinea pigs. METHODS: Two groups of guinea pigs (1-mo and 3-y old; n=40 each) were studied. Each group was divided into four subgroups of 10 animals each; one subgroup received lithogenic diet, one each received CCK or erythromycin daily in addition to lithogenic diet for 4 weeks, and one received normal diet. After 4 weeks, the presence of gallstones or sludge was recorded and bile composition including concentrations of bile acid, cholesterol, lecithin and protein concentrations was studied. RESULTS: No gallstones were observed in the 1-mo-old animals. In the 3-year-old animals, 9 of 10 guinea pigs on lithogenic diet and 4 of 10 in each treatment subgroup and the normal diet subgroup developed gallstones. CCK and erythromycin had similar effects on bile chemistry and stone formation. CONCLUSIONS: Aging increases the formation of gallstones in guinea pigs. Erythromycin is as effective as CCK in reducing gallstone formation by improving gall bladder motility.

Aging↗

[Erythromycin resistance of group A beta-hemolytic streptococci isolated from patients with upper respiratory tract infections].

The purpose of this study was to determine the erythromycin resistance of group A beta-hemolytic streptococci (GABHS) isolated from throat cultures. GABHS were isolated from 74 (10.4%) throat cultures of 710 patients with upper respiratory tract infections. Penicillin resistance was observed in none of the strains. Of these strains, 4 (5.4%) were found to be resistant to erythromycin. It was concluded that erythromycin resistance in GABHS, although high in some countries, was not a problem in our country at the moment. So, penicillin G and its alternative erythromycin and other macrolides are still reliable antibiotics for the treatment of GABHS infections.

Anti-Bacterial Agents↗

Anti-inflammatory effects of erythromycin and tetracycline on Propionibacterium acnes induced production of chemotactic factors and reactive oxygen species by human neutrophils.

Propionibacterium acnes (P. acnes), an anaerobic pathogen, plays an important role in the pathogenesis of acne and seems to initiate the inflammatory process by producing neutrophil chemotactic factors (NCF). Once neutrophils attracted by bacterial chemoattractants reach the inflamed site, they release inflammatory mediators such as lysosomal enzymes and reactive oxygen species (ROS). Previously, it has been shown that antibiotics may affect acne by means other than their anti-bacterial effects. Thus, we investigated the effect of subminimal inhibitory concentration (sub-MIC) of tetracycline and erythromycin on production of NCF and ROS. NCF was tested in vivo in a mouse model and ROS was estimated on human PMNL in vitro, by nitroblue tetrazolium dye reduction test (NBT) and cytochrome-C reduction test. Tetracycline (CS-T) and Erythromycin (CS-E) treated cultures showed a significant reduction of 35.8% and 58.3% in NCF production respectively, as compared to P. acnes stimulated cultures. Tetracycline and erythromycin at their sub-MIC also significantly inhibited release of ROS from human PMNL. Thus, tetracycline and erythromycin, besides having antibacterial activity, also have an anti-inflammatory action. These antibiotics reduce the capacity of P. acnes to produce NCF, as well decrease its ability to induce ROS from PMNL.

Acne Vulgaris↗

[A clinical study of the long-term therapeutic effects of low-dose erythromycin in diffuse panbronchiolitis--with special reference to changes in tumor-associated carbohydrate antigens in serum].

We investigated the long-term (3-30 months) therapeutic effects of low-dose (300-600 mg/day) erythromycin in 26 patients with diffuse panbronchiolitis (DPB). Significant improvements of pulmonary functions especially in %VC and PaO2 as well as respiratory symptoms were shown. However, erythromycin treatment was not associated with a significant change in surface phenotypes on peripheral blood lymphocytes (CD4, CD8, CD4/CD8). It is well known that serum levels of tumor-associated carbohydrate antigens such as SLX (sialylated Lewis X-i) and CA19-9 (sialylated Lewis(a)) are significantly elevated in patients with DPB. In the present study, 68.4% (13/19) of DPB patients showed marked elevation of SLX and 52.9% (9/17) showed marked elevation of CA19-9 levels in serum. These positive ratios were significantly decreased by erythromycin treatment to 31.6% (6/19) in SLX and 23.4% (4/17) in CA19-9. The mean values of each marker were also significantly decreased after erythromycin administration from 54.9 +/- 26.9 U/ml to 39.5 +/- 22.1 U/ml for SLX and from 70.5 +/- 77.4 U/ml to 28.8 +/- 37.4 U/ml for CA19-9.

Adolescent↗

Erythromycin accelerates delayed gastric emptying of solids in patients after truncal vagotomy and pyloroplasty.

OBJECTIVE: To find out if erythromycin (a motilin agonist) accelerated gastric emptying after vagotomy and in normal subjects. DESIGN: Double blind controlled study. SETTING: Two referral centres. SUBJECTS: 15 patients who had previously undergone vagotomy and who did (n = 8) or did not (n = 7) have symptoms of gastric stasis and 10 normal controls. INTERVENTIONS: A standard meal containing 185 x 10(5) Bq -99mTc was eaten after either erythromycin 200 mg or 40 ml placebo (normal saline) had been given intravenously. Subjects were then scanned by gamma camera. MAIN OUTCOME MEASURES: Measurement of: the length of time from completion of the meal to the onset of gastric emptying; the length of time from completion of the meal until half of the meal had left the stomach; the length of the time from the onset of gastric emptying until half of the meal had left the stomach; and the percentage of the meal that was left in the stomach at 60 and 120 min after the end of the meal. RESULTS: Gastric emptying was significantly delayed in those patients with symptoms compared with normal subjects and patients without symptoms. Erythromycin accelerated the first two phases of gastric emptying in all patients and normal subjects, but did not affect the length of time from the onset of gastric emptying until half the meal had left the stomach. CONCLUSION: Erythromycin could be a useful gastrokinetic agent in patients with symptoms of gastric stasis after vagotomy.

Adult↗

[Effect of erythromycin on the expression of apoptotic gene on eosinophils in nasal polyps in vitro].

OBJECTIVE: To study the expression of apoptotic gene in nasal polyps and the possible effect of erythromycin on it. METHODS: Total 40 nasal polyps biopsies were detected the expression of Bcl-2, Bax, Bcl-xL as well as Fas protein on eosinophils by immunohistochemistry. The expression of Bax, Bcl-xL, Fas on eosinophils in 15 nasal polyps explants which cultured with or without erythromycin were detected also. RESULTS: In nasal polyps, the expression of Bcl-2, Bax, Bcl-xL and Fas protein on eosinophils are 5% (2/10), 65% (26/40), 40% (16/40) and 90% (36/40) respectively. As compared with inferior turbinate, there were significant difference in expression of Bax and Fas protein between two tissues (P < 0.05). After cultured with erythromycin, the expression of Bax protein increased (P < 0.05), but the expression of Bcl-xL and Fas protein had not changed. CONCLUSION: Bax may be the most significant gene which control the apoptosis of eosinophils in nasal polyps. And a possible mechaism which erythromycin promote the apoptosis of eosinophils is increase the expression of Bax.

Adolescent↗

Identification of a single base change in ribosomal RNA leading to erythromycin resistance.

The molecular basis of a mutation conferring an erythromycin-resistance phenotype was explored, as an approach to the role of 23 S rRNA in the peptidyl-transferase activity of 50 S ribosomal subunits. Mutagenization of an Escherichia coli strain, which carried the multicopy plasmid pLC7-21 containing the rrnH operon, led to the production of an erythromycin-resistant strain. Plasmid pBFL1 isolated from this mutant was able to transform the sensitive RecA- strain EM4 and to induce a "dissociated" type of antibiotic resistance. Two ribosome populations occurred in EM4/pBFL1: normal particles coded for by the seven rrn chromosomal genes and mutated particles containing rRNA of plasmid origin. The latter particles displayed in vitro lower affinity and susceptibility to erythromycin than wild type particles. The mutation within plasmid pBFL1 was mapped by a multiple primer extension technique. Three synthetic primers were used to sequence the central loop in domain V of 23 S rRNA, leading to identification of a C to U transition at position 2611. This base change was proved to be responsible for the erythromycin-resistance phenotype by the plasmid-plasmid marker rescue technique. A molecular explanation for the rrn mutations leading, respectively, to undissociated and to dissociated types of resistance to the MLSb (macrolide-lincosamide-synergimycin B) group of antibiotics is proposed. These results and some literature data support the notion that rRNA bases involved in antibiotic resistance play a conformational role in the ribosomal binding sites for the MLSb antibiotics.

Base Sequence↗

[Differentiation of resistance phenotypes among erythromycin-resistant streptococci].

Although macrolide antibiotics have proved to be a valuable alternative to beta-lactam antibiotics in the treatment of respiratory tract infections, resistance to these agents is now becoming established in streptococci, especially among Streptococcus pneumoniae isolates. Of particular concern is the emergence of cross-resistance to 14-, 15- and 16-membered macrolides, licosamides and group B streptogramins (MLSb phenotype). MLS resistance can be expressed either constitutively (cMLS phenotype) or inducibly (iMLS phenotype). MLS resistance is mediated by two classes of methylase genes--the conventional erm(B) and recently described erm(A) determinants. A new macrolide efflux mechanism has been described for streptococci, in which it is associated with a new resistance pattern (M phenotype) characterized by resistance to 14- and 15-membered macrolides, and susceptibility to 16-membered macrolides, lincosamides and streptogramin B. The recognition of the prevalence of M phenotype in streptococci has implications for sensitivity testing and may have an impact on the choice of antibiotic therapy in clinical practice. While M resistance is similar in S. pyogenes and S. pneumoniae being mediated by mef(A) and mef(E), respectively, MLS resistance in both species appears to be genotypically and phenotypically more varied. Differentiation of M and MLS phenotypes of erythromycin-resistant strains can be performed using the erythromycin-clindamycin double-disc method (ECDD). Distinguishing not only M resistance but also constitutively or inducibly MLS phenotype by ECDD in S. pyogenes is easily and reliably achieved. Inducible MLS phenotype S. pyogenes strain is genotypically and phenotypically heterogeneous and is further subdivided into three recently described subtypes, iMLS-A, iMLS-B and iMLS-C, by a triple-disk test with erythromycin plus clindamycin and josamycin. While distinguishing M from MLS resistance in S. pneumoniae by ECDD test is easily and reliably achieved, the differentiation between constitutive and inducible MLS resistance is by far more uncertain. The meaning of inducible MLS resistance appears to be different in S. pneumoniae from that in S. pyogenes. In order to easily differentiate, within erythromycin-resistant pneumococci, not only the strains of the M phenotype from those with MLS resistance but also among the latter, cMLS from iMcLS strains, a triple-disk test has been set up by adding a rokitamycin disk to the conventional

Drug Resistance, Bacterial↗

[Correlation of HERG K+ channel protein expression to chemosensitivity of tumor cells to doxorubicin and its modulation by erythromycin].

BACKGROUND & OBJECTIVE: Previous studies have found that HERG, a kind of K(+) channel protein, is expressed in some cancers, but its expression is weak or lost in normal tissues. This study was to investigate HERG expression in various cancer cell lines, its correlation with chemosensitivity of cancer cells to doxorubicin, and its biochemical modulation. METHODS: HERG expression in human colon carcinoma cell line HT-29, human breast carcinoma cell line MCF-7, human lung carcinoma cell line A549, and human high-metastatic giant cell lung carcinoma cell line PG was analyzed by Western blot. After transfection of herg gene, the cytotoxicity of doxorubicin, erythromycin (a HERG K+ channel blocker), or doxorubicin in combination with erythromycin to cancer cells was analyzed by MTT assay. Intracellular content of doxorubicin was observed under fluorescent microscope. RESULTS: HERG protein level was higher in HT-29, MCF-7, and PG cells than in A549 cells. A549 cells were more sensitive to doxorubicin than HT-29 cells. The 50% inhibitory concentration (IC(50)) of doxorubicin was obviously higher in herg-transfected A549 cells than in parent A549 cells. Erythromycin obviously suppressed the growth of HT-29 cells, and showed synergic cytotoxicity with doxorubicin to HT-29 cells. There is no difference in intracellular doxorubicin content among herg-transfected A549 cells, pCDNA3.1-transfected A549 cells, and parent A549 cells. CONCLUSIONS: HERG expression might negatively correlate with the chemosensitivity of tumor cells to doxorubicin. Erythromycin may act as a modulator, and has synergic effect with doxorubicin. HERG may serve as a molecular marker and modulating target for individualized cancer therapy.

Antibiotics, Antineoplastic↗

[Synthesis of derivatives of (9S)-12-methylene erythromycin and their antibacterial activity in vitro].

AIM: To synthesizs of derivatives of (9S)-12-methylene erythromycin possessed potent antibacterial activity. METHODS: Using erythromycin A as a starting material, via two intermediate compounds protected 12,21-dehydroerythromycin A and 6,7: 12,21-didehydro erythromycin A, several 9-O, 11-O-ethylidene compounds were obtained. During this process, benzyl and isopropyl have been selected as the protecting group. The structures of compounds obtained were confirmed with 13C NMR and MS-FAB. Their antibacterial activity in vitro was tested. RESULTS: Eleven derivatives of erythromycin were synthesized. Five of them were unknown compounds. CONCLUSION: The preliminary biological test showed that two target compounds exhibited less potent antibacterial activity in vitro.

Anti-Bacterial Agents↗

Characterization of erythromycin resistance of Streptococcus pyogenes isolated from pharyngitis patients in Korea.

Six hundred fifteen isolates of Streptococcus pyogenes were collected over a 6-year period from patients with pharyngitis in Korea. All isolates were characterized in terms of their antibiotic resistance, the phenotypes of erythromycin resistance, the frequencies of erm(B), erm(A), and mef(A) genes, and the emm genotype. The prevalent emm genotypes were emm12 and emm4. Moreover, the emm12 genotype was found to be the most resistant strain to erythromycin. Among the 126 strains demonstrating resistance to erythromycin, those with erm(B) were the most prevalent, accounting for 64.3% of the total. In summary, it is suggested that the S. pyogenes pathogen isolated from pharyngitis patients in Korea developed resistant gene acquisition, as well as a resistant phenotype, according to the annual prevailing emm type. It is also suggested that the emm genotype distribution of erythromycin-resistant strains is correlated to the acquisition of resistant genes.

Anti-Bacterial Agents↗

[Investigation of erythromycin resistance and resistance phenotypes in group A beta hemolytic streptococci].

Although penicillin resistance has not been determined in group A beta haemolytic streptococci (GABHS) yet, resistance to erythromycin and other macrolids is being reported frequently in the last years. In this study we investigated erythromycin resistance by using agar dilution method in 282 GABHS strains which were isolated from throat cultures that had been evaluated in the Ministry of Health, Ankara Training and Research Hospital's, Microbiology Laboratory. We also determined resistance phenotypes of resistant strains by double disc synergy method using erythromycin and clindamycin discs. Twelve of 282 strains (4.3%) were found resistant to erythromycin; five (41.7%) of which were M phenotype, four (33.3%) of which were constitutive type MLSB phenotype and three (25%) of which were inducible type MLSB phenotype. Investigation of resistance to macrolides that are alternatives to penicillin therapy in GABHS, is very important for the determination of the therapy and also to provide epidemiological data.

Anti-Bacterial Agents↗

Resistance to erythromycin and rising penicillin MIC in Streptococcus pyogenes in India.

There has been worldwide resurgence in the incidence of Streptococcus pyogenes infection and its sequelae. S. pyogenes remains uniformly susceptible to penicillin, and it is speculated that its minimum inhibitory concentration (MIC) has not changed during the past 70 years. The purpose of the present study was to determine the occurrence and pattern of resistance to penicillin and erythromycin amongst clinical isolates of S. pyogenes. A total of 34 clinical strains of S. pyogenes were identified by standard procedures. Antimicrobial susceptibility was analyzed by the Kirby-Bauer method of disk diffusion, and the E-test method was used to determine the MIC to penicillin and erythromycin. All the strains were sensitive to penicillin, clindamycin and vancomycin on disk diffusion. Ten (29.4%) strains were resistant to erythromycin. The pattern of macrolide resistance observed was M type. By the E-test method, 7 (20.6%) strains were penicillin nonsusceptible and 6 (17.6%) were erythromycin resistant. We concluded that surveillance of its susceptibility pattern is crucial to monitoring the development of antibiotic resistance in S. pyogenes.

Disk Diffusion Antimicrobial Tests↗

[Resistance to erythromycin in Streptococcus pneumoniae].

A total of 640 S. pneumoniae isolates from different clinical samples obtained from patients (not including carriers) over a 10 years period were studied. Global resistance to erythromycin (MIC greater than or equal to 1 microgram/ml) was 9.1% (8.1% with MIC greater than or equal to 8 micrograms/ml). Resistance was more prevalent in serotypes 6, 14, and 19, either in absolute number or in relation to the total number of strains in each serotype. A total of 16% of strains isolated from ear fluid specimens and bronchial secretions were resistant, but only a 4.5% of blood culture isolates showed also resistance to erythromycin. Resistance was found more frequently on pediatric patients. Although the highest resistance rate was found during the last year (15% of all 1990 isolated strains or 13.9% if the period also includes the first 1991 quarter) we did not find a gradual increase over time. Most of the resistant strains showed also resistance to tetracycline and other antimicrobial agents. Overall, 94.8% of strains showed multiple resistance (combined resistance to at least 2 other different antibiotics, not including clindamycin resistance, which always matches erythromycin resistance), and 60.3% showed resistance to penicillin. The multiply-resistant pattern and the similarity of isolated strains suggest an epidemiologic behaviour that not necessarily has to be linked to higher erythromycin use.

Adult↗