Concentrations Of Erythromycin Research Articles

Determination of selected human pharmaceutical compounds in effluent and surface water samples by high-performance liquid chromatography–electrospray tandem mass spectrometry

A simple method is presented for the analysis of 13 pharmaceutical and pharmaceutical metabolite compounds in sewage effluents and surface waters. The pharmaceutical compounds were extracted using a generic solid-phase extraction (SPE) procedure using Phenomenex Strata X as a stationary phase. Extracts were quantitatively analysed by four separate reversed-phase high-performance liquid chromatography–electrospray tandem mass spectrometry (HPLC–ESI-MS/MS) techniques and quantified by comparison with an internal standard ([ 13 C ]-phenacetin). Recoveries and limits of detection (LOD) for sulfamethoxazole (120%, 50 ng l −1), acetyl-sulfamethoxazole (56%, 50 ng l −1), trimethoprim (123%, 10 ng l −1), erythromycin (73%, 10 ng l −1), paracetamol (75%, 50 ng l −1), ibuprofen (117%, 20 ng l −1), clofibric acid (83%, 50 ng l −1), mefenamic acid (24%, 50 ng l −1), diclofenac (62%, 20 ng l −1), propranolol (45%, 10 ng l −1), dextropropoxyphene (63%, 20 ng l −1) and tamoxifen (42%, 10 ng l −1) were all acceptable. The recovery of lofepramine (4%) was too low to be of use in a monitoring programme. Application of the method to samples collected from UK sewage effluents and surface waters showed detectable concentrations of mefenamic acid, diclofenac, propranolol, erythromycin, trimethoprim and acetyl-sulfamethoxazole in both matrices. Ibuprofen and dextropropoxyphene were detected in sewage effluents alone. All other pharmaceutical compounds were below the methods limits of detection.

Selection of resistant Streptococcus pneumoniae during penicillin treatment in vitro and in three animal models.

Pharmacokinetic (PK) and pharmacodynamic (PD) properties for the selection of resistant pneumococci were studied by using three strains of the same serotype (6B) for mixed-culture infection in time-kill experiments in vitro and in three different animal models, the mouse peritonitis, the mouse thigh, and the rabbit tissue cage models. Treatment regimens with penicillin were designed to give a wide range of T(>MIC)s, the amounts of time for which the drug concentrations in serum were above the MIC. The mixed culture of the three pneumococcal strains, 10(7) CFU of strain A (MIC of penicillin, 0.016 micro g/ml; erythromycin resistant)/ml, 10(6) CFU of strain B (MIC of penicillin, 0.25 micro g/ml)/ml, and 10(5) CFU of strain C (MIC of penicillin, 4 micro g/ml)/ml, was used in the two mouse models, and a mixture of 10(5) CFU of strain A/ml, 10(4) CFU of strain B/ml, and 10(3) CFU of strain C/ml was used in the rabbit tissue cage model. During the different treatment regimens, the differences in numbers of CFU between treated and control animals were calculated to measure the efficacies of the regimens. Selective media with erythromycin or different penicillin concentrations were used to quantify the strains separately. The efficacies of penicillin in vitro were similar when individual strains or mixed cultures were studied. The eradication of the bacteria, independent of the susceptibility of the strain or strains or the presence of the strains in a mixture or on their own, followed the well-known PK and PD rules for treatment with beta-lactams: a maximum efficacy was seen when the T(>MIC) was >40 to 50% of the observation time and the ratio of the maximum concentration of the drug in serum to the MIC was >10. It was possible in all three models to select for the less-susceptible strains by using insufficient treatments. In the rabbit tissue cage model, a regrowth of pneumococci was observed; in the mouse thigh model, the ratio between the different strains changed in favor of the less-susceptible strains; and in the mouse peritonitis model, the susceptible strain disappeared and was overgrown by the less-susceptible strains. These findings with the experimental infection models confirm the importance of eradicating all the bacteria taking part in the infectious process in order to avoid selection of resistant clones.

Activity of telithromycin and seven other agents against 1034 pediatric Streptococcus pneumoniae isolates from ten central and eastern European centers

To test the activity of telithromycin against 1034 Streptococcus pneumoniae isolates from pediatric patients in ten centers from ten central and eastern European countries during 2000-2001, and to compare it with the activities of erythromycin A, azithromycin, clarithromycin, clindamycin, and quinupristin-dalfopristin. The minimum inhibitory concentrations (MICs) of telithromycin, erythromycin A, azithromycin, clarithromycin, clindamycin, levofloxacin, quinupristin-dalfopristin and penicillin G were tested by the agar dilution method with incubation in air, and mechanisms of resistance to macrolides and quinolones were investigated. Strains were isolated from sputum, tracheal aspirates, ear, eye, blood, and cerebrospinal fluid. Among S. pneumoniae strains tested, 36% had raised penicillin G MICs (>/= 0.12 mg/L). Susceptibilities were as follows: telithromycin, quinupristin-dalfopristin and levofloxacin, >/= 99%; clindamycin, 83%; and erythromycin A, azithromycin and clarithromycin, 78%. Of 230 (22.3%) erythromycin A-resistant S. pneumoniae strains, 176 (79.6%) had erm(B), 38 (16.1%) had mef(A), and 10 (4.3%) had mutations in 23S ribosomal RNA or in ribosomal protein L4. The rates of drug-resistant S. pneumoniae are high in all centers except Kaunas, Riga, and Prague. Telithromycin had low MICs against all strains, irrespective of macrolide, azalide or clindamycin resistance. Ribosomal methylation was the most prevalent resistance mechanism among all resistant strains, except in Sofia, where the prevalence of the efflux mechanism was higher.

Uptake of erythromycin by first-feeding sockeye salmon, Oncorhynchus nerka (Walbaum), fed live or freeze-dried enriched adult Artemia or medicated pellets.

The potential to use adult Artemia to deliver erythromycin to first-feeding sockeye salmon, Oncorhynchus nerka (Walbaum), was investigated in three trials. In the first trial, first-feeding sockeye were fed live erythromycin enriched adult Artemia or pellets containing equal amounts of erythromycin for 35 days. At the end of the trial, tissue erythromycin concentration of the fish fed the live Artemia was significantly greater (P < 0.05, 25.52 +/- 1.29 microg mL(-1); mean +/- SEM), than the tissue concentration of the fish fed the pellets (0.72 +/- 0.01 microg mL(-1)). In the second trial, first-feeding sockeye were fed either live or freeze-dried bioencapsulated erythromycin (adult Artemia) or pellets containing erythromycin daily for 21 days. Mean daily erythromycin concentration in fish fed the freeze-dried Artemia, live Artemia, or pellets did not differ significantly. In the third trial, apparent erythromycin digestibility was determined. Significantly more (P < 0.05) erythromycin was retained by juvenile sockeye fed freeze-dried bioencapsulated erythromycin (98.3 +/- 1.0%) compared with medicated pellets (89.2 +/- 1.7%). Uptake of bioencapsulated erythromycin from adult Artemia (live or freeze-dried) appears to be greater than uptake from pellets. Freeze-dried and live Artemia were equally effective at delivery suggesting enriched freeze-dried adult Artemia could be produced into a highly palatable, consistent, off-the-shelf product.

Plasmid-borne macrolide resistance in Micrococcus luteus.

A plasmid designated pMEC2 which confers resistance to erythromycin, other macrolides, and lincomycin was detected in Micrococcus luteus strain MAW843 isolated from human skin. Curing of this approximately 4.2 kb plasmid from the host organism resulted in erythromycin sensitivity of the strain. Introduction of pMEC2 into a different M. luteus strain conferred erythromycin resistance upon this strain. Macrolide resistance in M. luteus MAW843 was an inducible trait. Induction occurred at subinhibitory erythromycin concentrations of about 0.02-0.05 micro g ml(-1). Erythromycin and oleandomycin were inducers, while spiramycin and tylosin exerted no significant inducer properties. With heterologous expression experiments in Corynebacterium glutamicum, using hybrid plasmid constructs and deletion derivatives thereof, it was possible to narrow down the location of the plasmid-borne erythromycin-resistance determinant to a region of about 1.8 kb of pMEC2. Sequence analysis of the genetic determinant, designated erm(36), identified an ORF putatively encoding a 281-residue protein with similarity to 23S rRNA adenine N(6)-methyltransferases. erm(36) was most related (about 52-54% identity) to erythromycin-resistance proteins found in high-G+C Gram-positive bacteria, including the (opportunistic) pathogenic corynebacteria Corynebacterium jeikeium, C. striatum, C. diphtheriae and Propionibacterium acnes. This is believed to be the first report of a plasmid-borne, inducible antibiotic resistance in micrococci. The possible role of non-pathogenic, saprophytic micrococci bearing antibiotic-resistance genes in the spreading of these determinants is discussed.

Hatchery Evaluation of Erythromycin Phosphate Injections in Prespawning Spring Chinook Salmon

Abstract In a hatchery field trial, we evaluated the efficacy and safety of two sequential injections of erythromycin phosphate in prespawning spring chinook salmon Oncorhynchus tshawytscha. For dosing purposes, we used fish fork length to estimate weight based on a weight−length relationship for spring chinook salmon. All fish in the hatchery population (N = 1,568) were injected with one of two doses of erythromycin phosphate (20 mg/kg body weight or 40 mg/kg), followed 1 month later by a second injection of 20 mg/kg. We monitored the survival of fish after injection and determined the concentrations of erythromycin and soluble antigen of Renibacterium salmoninarum in the kidneys of each fish that survived to spawning. After the first injection, mortality was significantly higher among female fish administered 40 mg/kg than among female fish administered 20 mg/kg. The concentration of erythromycin in the kidneys of females at spawning was significantly higher than that in the kidneys of males, as was the...

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.

Bioencapsulation of five forms of erythromycin by adult Artemia salina (L.)

Uptake of five chemical forms of erythromycin by adult Artemia salina (L.) (erythromycin phosphate – EP, erythromycin stearate – ES, erythromycin estolate – EE, erythromycin hydrate – EH and crystalline erythromycin – CE) was investigated in two trials. In each trial, final erythromycin concentration in Artemia tissue and survival after a 12‐h bioencapsulation period were determined. In the first trial, Artemia tissue concentration after a 12‐h bioencapsulation period was significantly (P &lt; 0.05) affected by erythromycin form with ES (68.5 ± 3.3 μg mL−1, mean ± SEM) ≈ EH (61.2 ± 3.4 μg mL−1) &gt; CE (37.1 ± 10.7 μg mL−1) &gt; EP (16.4 ± 7.7 μg mL−1) &gt; control. In trial 2, Artemia tissue concentration was also significantly (P &lt; 0.05) affected by erythromycin form with EE (111.4 ± 9.6 μg mL−1) &gt; CE (89.1 ± 1.7 μg mL−1) &gt; ES (78.9 ± 1.6 μg mL−1) &gt; EP (33.4 ± 5.2 μg mL−1) &gt; control. Survival was significantly affected by erythromycin form in trial 1 with EP=control (100 ± 0.0%) &gt; ES (74.4 ± 2.0%) &gt; CE (32.2 ± 0.3%) &gt; EH (8.8 ± 4.4%). In trial 2, survival was also significantly affected by erythromycin form with EP=control (100 ± 0.0%) &gt; ES (67.1 ±3.7%) &gt; CE (52.5 ± 7.7%) &gt; EE (5.0 ± 2.5%). Based on both uptake and survival, EP and ES appear to be appropriate compounds for bioencapsulation of erythromycin using live adult Artemia.

Erythromycin susceptibility of viridans streptococci from the normal throat flora of patients treated with azithromycin or clarithromycin

Objective To study the emergence of macrolide resistance in throat flora following treatment with clarithromycin or azithromycin.Methods Throat samples were collected before and after treatment and plated as a lawn on Columbia blood agar with an erythromycin E test strip. Minimum inhibitory concentrations (MICs) of erythromycin, clarithromycin and azithromycin were determined against isolates of distinct morphology with erythromycin E test MIC results equal to or greater than 2 mg/L. Polymerase chain reaction techniques were used to determine the genetic mechanisms of resistance.Results There were 749 resistant isolates of which 474 (63%) were streptococci. Only a quarter of the patients had no resistant streptococci before treatment started. There were increases in the numbers of resistant isolates and in the number of patients carrying a resistant flora during and after treatment. The most common genes identified were mefA/E in isolates with low-level resistance and ermA/M in isolates with high-level resistance.Conclusions There is a pool of streptococci carrying genes associated with macrolide resistance in the normal respiratory flora of generally healthy adults. Differences between the patients treated with clarithromycin and those treated with azithromycin were difficult to assess because of the large number of patients in each group with macrolide-resistant streptococci before treatment. Although there were some differences these were not statistically significant.

Inhibition of Lipase Activity in Antibiotic-Resistant Propionibacterium acnes Strains

Background and Objective: Erythromycin-sensitive and/or clindamycin-sensitive strains of Propionibacterium acnes show a reduced lipase production at levels below the minimal growth-inhibitory concentration (MIC). The objective of this study was to determine whether erythromycin and clindamycin concentrations far below the MIC inhibit lipase production in P. acnes strains resistant to these antibiotics. Methods: Of 42 P. acnes strains, 10 showed an MIC >256 µg/ml for erythromycin. Two strains showed MICs of 0.19 and 0.25 µg/ml, while the MIC of the remaining strains was ≤0.016 µg/ml. Lipase activity was determined up to a concentration of 192 µg/ml by cultivation on spirit blue agar + lipase reagent. The 10 strains whose erythromycin MIC was >256 µg/ml were also tested for lipase inhibition by clindamycin. While this method fails to differentiate between inhibition of lipase production and inhibition of lipase activity, the absence of inhibition of lipase activity rules out inhibition of lipase production. Results: Inhibition of lipolysis by sub-MIC concentrations was demonstrated only for clindamycin in 3 P. acnes strains. However, lipase inhibition was seen only at the dilution level immediately below the MIC. Conclusions: Resistant P. acnes strains with high erythromycin and/or clindamycin MICs can be ruled out to show in vitro inhibition of lipase production at antibiotic concentrations far below the MIC.

Intravenous low-dose erythromycin administration for infants with feeding intolerance.

This study was undertaken to determine the efficacy of low-dose intravenous erythromycin (EM) administration in infants with feeding intolerance. The subjects were 26 infants who would not accept enteral feeding within 5 days after birth. Fourteen infants (gestational age: 30.6+/-5.4 weeks and birthweight: 1466+/-825 g) were given EM intravenously at a dose of 1 mg/kg, three times daily (EM group). Doses were increased to 2 mg/kg in five infants who showed a poor response. Twelve infants (gestational age: 30.5+/-5.0 weeks and birthweight: 1317+/-672 g) were observed without EM administration (non-EM group). Blood concentrations of EM at 2 h after administration were measured on 8 (+/-2) days after the start of EM administration in the EM group. Digestive perturbations and intestinal gasless and/or atonic shadows on X-ray findings markedly improved in the EM group soon after the treatment. Comparing the EM group and non-EM group, the postnatal ages at the start of successful enteral feeding were 9.1+/-3.2 days and 14.0+/-4.1 days, respectively (P<0.01). The postnatal ages at feeding of 100 mL/kg per day were 15.2+/-4.0 days and 23.4+/-6.2 days, respectively (P<0.01). The blood EM concentrations of 1 mg/kg and 2 mg/kg were 0.29+/-0.28 microg/mL and 0.57+/-0.20 microg/mL, respectively (P<0.05). No adverse effect on cardiac status or in blood examinations was observed in any infant in the EM group. These results suggest that intravenous low-dose EM administration is a useful and safe treatment of feeding intolerance in infants including extremely low-birthweight infants.

The Effect of Erythromycin on Mucociliary Transportability and Rheology of Cystic Fibrosis and Bronchiectasis Sputum

Background: Erythromycin has been shown to diminish sputum production in hypersecretory states by a mechanism that is still unclear. Objectives and Methods: We have investigated the effect of erythromycin on the ciliary transportability of cystic fibrosis and non-cystic fibrosis bronchiectasis sputum in vitro using the mucus-depleted bovine trachea. Results: Additional erythromycin in concentrations up to 20 µg/g did not significantly alter the ciliary transportability of sputum from 6 cystic fibrosis and 6 bronchiectasis patients. Sputum viscoelasticity measured with parallel-plate rheology was also little changed. These erythromycin concentrations also had little effect on the beating frequency of bovine tracheal cilia. Conclusions: These results suggest that the presence of erythromycin in sputum neither alters the physical properties of the gel nor the activity of cilia. The clinical effects of erythromycin on pulmonary hypersecretory states therefore have another explanation.

Pharmacokinetic-pharmacodynamic modeling of the inhibitory effect of erythromycin on tumour necrosis factor-alpha and interleukin-6 production.

Erythromycin inhibits the production of tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL6) induced by heat-killed Streptococcus pneumoniae in human whole blood ex-vivo. The objective of the present study was to determine and characterize the concentration-effect relationship of this phenomenon in order to predict its possible clinical relevance. Six healthy volunteers received a single intravenous dose of 1000 mg erythromycin. Blood samples were obtained up to 4 h after drug administration. Samples were assayed for erythromycin concentrations and (after heat-killed Streptococcus pneumoniae stimulation) for TNF-alpha and IL6 concentrations. Effect vs. time data from individual subjects were fitted to the indirect response model with an Emax concentration-effect relationship. Simulations of these effects were performed for therapeutic intravenous and oral erythromycin dosage regimens. The geometric means of the values of Kin, Kout and EC50 were 15.4 microg/h, 0.82/h, 9.4 mg/L for TNF-alpha and 321 microg/h, 2.02/h, 18.3 mg/L for IL6. Simulations revealed a maximal inhibition of TNF-alpha concentrations of 35%, 50%, 16% and 27% at erythromycin dosages of 500 mg i.v., 1000 mg i.v., 500 mg p.o and 1000 mg p.o. q 6 h, respectively, whereas a maximal inhibition of IL6 of 29%, 44%, 13% and 22% are predicted for the respective regimens. The inhibitory effect of erythromycin on TNF-alpha and IL6 production can be adequately described by the indirect response model with an Emax concentration-effect relationship. Simulations predicted a substantial decrease of production of these cytokines at intravenous and to a much lesser extent at oral erythromycin dosage regimens.

Concentração mínima inibitória de dez antimicrobianos para amostras de Staphylococcus aureus isoladas de infecção intramamária bovina

Determinou-se a concentração mínima inibitória (CMI) de ampicilina, cefalotina, eritromicina, gentamicina, neomicina, norfloxacina, oxacilina, penicilina G, tetraciclina e tilosina para 112 amostras de Staphylococcus aureus isoladas de infecções intramamárias bovina, em 33 rebanhos leiteiros da Zona da Mata do Estado de Minas Gerais. Foram isoladas 24 amostras de infecção clínica, 66 de subclínica e 22 de infecção crônica. As amostras de infecção crônica foram isoladas repetidas vezes dos mesmos quartos mamários de nove vacas de um rebanho, no período de 13 meses. A CMI foi realizada em ágar Mueller Hinton, com concentrações entre 0,015 e 128µgml-1 de cada antimicrobiano. As amostras da American Type Culture Collection (ATCC) recomendadas para controle de qualidade, S. aureus ATCC 29213, Escherichia coli ATCC 25922 e Pseudomonas aeruginosa ATCC 27853, foram incluídas em cada teste. Cem por cento das amostras foram susceptíveis à cefalotina, eritromicina, gentamicina, norfloxacina e oxacilina, 91% à tetraciclina (CMI50: 0,5µgml-1) e à tilosina (CMI50: 2,0µgml-1), 65% à ampicilina (CMI50: 0,125µgml-1) e à penicilina G (CMI50: 0,06µgml-1). Todas foram susceptíveis à neomicina (CMI50: 0,5µgml-1) exceto uma amostra que apresentou um padrão intermediário. O nível de resistência para ampicilina e penicilina foi maior nas amostras isoladas de casos clínicos e nas de infecção subclínica com escores positivos no CMT (P&lt;0,02). Nas isoladas de infecção clínica, o nível de resistência à tilosina foi maior (P&lt;0,02). As amostras que apresentaram CMI &gt; ou = 0,125µgml-1 para penicilina foram positivas para produção de beta-lactamase.

Erythromycin inhibits Pseudomonas aeruginosa-induced tumour necrosis factor-alpha production in human whole blood.

Erythromycin has been shown to be beneficial for panbronchiolitis, a disorder linked to infection with Pseudomonas aeruginosa. Erythromycin, but not the anti-Pseudomonas antibiotics imipenem, ceftazidime, gentamicin and ciprofloxacin, caused a dose-dependent decrease in the production of tumour necrosis factor (TNF)-alpha by whole blood stimulated with heat-killed P. aeruginosa. The release of interleukin (IL)-10, IL-6, interferon-gamma and IL-8 was inhibited only at the highest erythromycin concentration. Inhibition of TNF-alpha production by erythromycin may, at least in part, explain the efficacy of this macrolide during panbronchiolitis despite its lack of activity for P. aeruginosa.

Differentiation of resistance phenotypes among erythromycin-resistant Pneumococci.

Laboratory differentiation of erythromycin resistance phenotypes is poorly standardized for pneumococci. In this study, 85 clinical isolates of erythromycin-resistant (MIC > or = 1 microg/ml) Streptococcus pneumoniae were tested for the resistance phenotype by the erythromycin-clindamycin double-disk test (previously used to determine the macrolide resistance phenotype in Streptococcus pyogenes strains) and by MIC induction tests, i.e., by determining the MICs of macrolide antibiotics without and with pre-exposure to 0.05 microg of erythromycin per ml. By the double-disk test, 65 strains, all carrying the erm(AM) determinant, were assigned to the constitutive macrolide, lincosamide, and streptogramin B resistance (cMLS) phenotype, and the remaining 20, all carrying the mef(E) gene, were assigned to the recently described M phenotype; an inducible MLS resistance (iMLS) phenotype was not found. The lack of inducible resistance to clindamycin was confirmed by determining clindamycin MICs without and with pre-exposure to subinhibitory concentrations of erythromycin. In macrolide MIC and MIC-induction tests, whereas homogeneous susceptibility patterns were observed among the 20 strains assigned to the M phenotype by the double-disk test, two distinct patterns were recognized among the 65 strains assigned to the cMLS phenotype by the same test; one pattern (n = 10; probably that of the true cMLS isolates) was characterized by resistance to rokitamycin also without induction, and the other pattern (n = 55; designated the iMcLS phenotype) was characterized by full or intermediate susceptibility to rokitamycin without induction turning to resistance after induction, with an MIC increase by more than three dilutions. A triple-disk test, set up by adding a rokitamycin disk to the erythromycin and clindamycin disks of the double-disk test, allowed the easy differentiation not only of pneumococci with the M phenotype from those with MLS resistance but also, among the latter, of those of the true cMLS phenotype from those of the iMcLS phenotype. While distinguishing MLS from M resistance in pneumococci is easily and reliably achieved, the differentiation of constitutive from inducible MLS resistance is far more uncertain and is strongly affected by the antibiotic used to test inducibility.

Effect of erythromycin on matrix metalloproteinase-9 and cell migration

Erythromycin (EM) has an anti-inflammatory effect that may account for its clinical benefit in the treatment of chronic inflammatory diseases such as diffuse panbronchiolitis. To investigate the mechanism of this anti-inflammatory effect, we studied the relationship between the concentration of EM and matrix metalloproteinase-9 (MMP-9) activity, which is important in cell migration. We showed that EM suppressed the gelatinolytic activity of U937 cell–derived MMP-9 by using gelatin zymography, showed that expressions of MMP-9 protein and MMP-9 mRNA were down-regulated by EM in a dose-dependent manner, and showed that U937 migration was also suppressed by EM. We also demonstrated that EM treatment suppressed the gelatinolytic activity of MMP-9 in spleen macrophages. These findings suggest that the suppressive effect of EM on MMP-9 activity is one of the anti-inflammatory mechanisms that inhibit the migration of inflammatory cells into the inflammatory site. (J Lab Clin Med 2000;137:176-83)

Macrolide resistance conferred by base substitutions in 23S rRNA.

Macrolide resistance conferred by base substitutions in 23S rRNA.

Antagonism between penicillin and erythromycin against Streptococcus pneumoniae in vitro and in vivo

The combination of beta-lactam antibiotics and macrolides is often recommended for the initial empirical treatment of acute pneumonia in order to obtain activity against the most important pathogens. Theoretically, this combination may be inexpedient, as the bacteriostatic agent may antagonize the effect of the bactericidal agent. In this study, the possible interaction between penicillin and erythromycin was investigated in vitro and in vivo against four clinical isolates of Streptococcus pneumoniae with MICs of penicillin ranging from 0.016 to 0.5 mg/L and of erythromycin from 0. 25 to >128 mg/L. In vitro time-kill curves were generated with clinically relevant concentrations of penicillin (10 mg/L) and erythromycin (1 mg/L), either individually or in combination. Antagonism between penicillin and erythromycin was observed for the four isolates. In vivo interaction was investigated in the mouse peritonitis model. After intraperitoneal inoculation, penicillin and erythromycin were given either individually or in combination. For two of the four isolates, mortality was significantly higher in the groups treated with the combination of penicillin and erythromycin than in the groups treated with penicillin alone [32/36 (86%) vs. 3/12 (25%), P<0.05; and 24/36 (67%) vs. 3/12 (25%), P<0.05, respectively]. Using the mouse peritonitis model, in vivo time-kill curves showed that there was antagonism between erythromycin and penicillin for the examined isolate. The antagonism demonstrated in vitro and in vivo between penicillin and erythromycin suggests that ss-lactam antibiotics and macrolides should not be administered together unless pneumococcal infection is ruled out.

Effect of subinhibitory antibiotic concentrations on polysaccharide intercellular adhesin expression in biofilm-forming Staphylococcus epidermidis.

Biofilm production is an important step in the pathogenesis of Staphylococcus epidermidis polymer-associated infections and depends on the expression of the icaADBC operon leading to the synthesis of a polysaccharide intercellular adhesin. A chromosomally encoded reporter gene fusion between the ica promoter and the beta-galactosidase gene lacZ from Escherichia coli was constructed and used to investigate the influence of both environmental factors and subinhibitory concentrations of different antibiotics on ica expression in S. epidermidis. It was shown that S. epidermidis biofilm formation is induced by external stress (i.e., high temperature and osmolarity). Subinhibitory concentrations of tetracycline and the semisynthetic streptogramin antibiotic quinupristin-dalfopristin were found to enhance ica expression 9- to 11-fold, whereas penicillin, oxacillin, chloramphenicol, clindamycin, gentamicin, ofloxacin, vancomycin, and teicoplanin had no effect on ica expression. A weak (i.e., 2.5-fold) induction of ica expression was observed for subinhibitory concentrations of erythromycin. The results were confirmed by Northern blot analyses of ica transcription and quantitative analyses of biofilm formation in a colorimetric assay.