Emycin-E purified from Streptomyces sp. RG1011 from Himalayan soil has antibiofilm activity against Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus is an opportunistic pathogen that causes deadly infections in human as well as animals. The intricate network of virulence factors and biofilms are the major hindrance for the antibiotics in the successful treatment of the infection. The aim of this study is to isolate, identify and characterize natural antimicrobial agent against S. aureus from natural resources. METHODS: Himalayan soils were subjected to primary, secondary and tertiary screening to isolate soil Actinobacteria. Identification and characterization of the isolate was done by various biochemical assays and 16s rDNA sequencing. Partial purification of the potent antimicrobial agent was done by n-butanol from the culture supernatant, TLC and HPLC were performed to purify the active component and subjected to FTIR and ESI-MS analysis. RESULTS: The potent isolate RM-1(13) was confirmed as Streptomyces griseus strain RG1011 (NCBI accession no: 0M780275) by biochemical and molecular analysis. The partially purified antimicrobial agent was active against various Gram-positive and Gram-negative pathogens. The active component was purified by HPLC and identified as Emycin-E by ESI-MS analysis. The Emycin-E has calculated MIC of 0.31 µg/ml against S. aureus ATCC 25923. Emycin-E inhibits the biofilm formation of S. aureus in in vitro microtiter plate assay. CONCLUSIONS: The identified antimicrobial agent was found active against various Gram-positive and Gram-negative pathogens. We have successfully identified the active compound as Emycin-E by FTIR and ESI-MS analysis. Our study suggests the role of Emycin-E in the inhibition of biofilm formation in S. aureus.

Translational Research Symposium-collaborative efforts as driving forces of healthcare innovation.

The 5th Translational Research Symposium was organised at the annual meeting of the European Society for Biomaterials 2018, Maastricht, the Netherlands, with emphasis on the future of emerging and smart technologies for healthcare in Europe. Invited speakers from academia and industry highlighted the vision and expectations of healthcare in Europe beyond 2020 and the perspectives of innovation stakeholders, such as small and medium enterprises, large companies and Universities. The aim of the present article is to summarise and explain the main statements made during the symposium, with particular attention on the need to identify unmet clinical needs and their efficient translation into healthcare solutions through active collaborations between all the participants involved in the value chain.

Effects of curcumin on the pharmacokinetics of tamoxifen and its active metabolite, 4-hydroxytamoxifen, in rats: possible role of CYP3A4 and P-glycoprotein inhibition by curcumin.

The effects of curcumin, a natural anti-cancer compound, on the bioavailability and pharmacokinetics of tamoxifen and its metabolite, 4-hydroxytamoxifen, were investigated in rats. Tamoxifen and curcumin interact with cytochrom P450 (CYP) enzymes and P-glycoprotein, and the increase in the use of health supplements may result in curcumin being taken concomitantly with tamoxifen as a combination therapy to treat or prevent cancer. A single dose of tamoxifen was administered orally (9 mg x kg(-1)) with or without curcumin (0.5, 2.5 and 10 mg x kg(-1)) and intravenously (2mg x kg(-1)) with or without curcumin (2.5 and 10 mg x kg(-1)) to rats. The effects of curcumin on P-glycoprotein (P-gp) and CYP3A4 activity were also evaluated. Curcumin inhibited CYP3A4 activity with 50% inhibition concentration (IC50) values of 2.7 microM. In addition, curcumin significantly (P < 0.01 at 10 microM) enhanced the cellular accumulation of rhodamine-123 in MCF-7/ADR cells overexpressing P-gp in a concentration-dependent manner. This result suggested that curcumin significantly inhibited P-gp activity. Compared to the oral control group (given tamoxifen alone), the area under the plasma concentration-time curve (AUC(0-infinity)) and the peak plasma concentration (C(max)) of tamoxifen were significantly (P < 0.05 for 2.5 mg x kg(-1); P < 0.01 for 10 mg x kg(-1)) increased by 33.1-64.0% and 38.9-70.6%, respectively, by curcumin. Consequently, the absolute bioavailability of tamoxifen in the presence of curcumin (2.5 and 10 mg x kg(-1)) was 27.2-33.5%, which was significantly enhanced (P < 0.05 for 2.5 mg x kg(-1); P < 0.01 for 10 mg x kg(-1)) compared to that in the oral control group (20.4%). Moreover, the relative bioavailability of tamoxifen was 1.12- to 1.64-fold greater than that in the control group. Furthermore, concurrent use of curcumin significantly decreased (P < 0.05 for 10 mg x kg(-1)) the metabolite-parent AUC ratio (MR), implying that curcumin may inhibit the CYP-mediated metabolism of tamoxifen to its active metabolite, 4-hydroxytamoxifen. The enhanced bioavailability of tamoxifen by curcumin may be mainly due to inhibition of the CYP3A4-mediated metabolism of tamoxifen in the small intestine and/or in the liver and to inhibition of the P-gp efflux transporter in the small intestine rather than to reduction of renal elimination of tamoxifen, suggesting that curcumin may reduce the first-pass metabolism of tamoxifen in the small intestine and/or in the liver by inhibition of P-gp or CYP3A4 subfamily.

Comparison of the effect of azithromycin versus erythromycin on antroduodenal pressure profiles of patients with chronic functional gastrointestinal pain and gastroparesis.

BACKGROUND: Current pharmacologic treatments for gastroparesis have been disappointing due to the limited options available. Erythromycin ethylsuccinate is a potent prokinetic agent that stimulates gastric emptying. Recently, erythromycin has been linked to the occurrences of sudden cardiac death due to QT prolongation. Azithromycin is similar to erythromycin in structure but does not have significant drug-drug interactions as seen with erythromycin. PURPOSE: This study aims to determine whether azithromycin stimulates antral activity in patients with chronic gastrointestinal pain and refractory gastroparesis. METHODS: Small bowel manometric data on 30 patients undergoing clinical evaluation for chronic digestive problems or documented refractory gastroparesis were reviewed. Antral activity was measured after infusion of erythromycin 250 mg intravenous and azithromycin (500 or 250 mg intravenous) given at different intervals during the small bowel manometry. The parameters measured included the total duration of effect, mean amplitude of antral contractions, duration of the highest antral contraction phase, number of cycles per minute, and the motility index. RESULTS: Comparison of erythromycin and azithromycin at similar doses showed a similar positive effect on antral activity. However, comparison of erythromycin and azithromycin at the higher dose of 500 mg showed that the mean amplitude, duration of antral activity, and motility index were significantly increased with azithromycin (P < 0.05). CONCLUSIONS: Azithromycin stimulates antral activity similar to erythromycin and moreover has a longer duration of effect. However, unlike erythromycin, azithromycin does not have significant drug-drug interactions and maybe a potential new medication for the treatment of gastroparesis and gastrointestinal dysmotility.

Sensitive determination of tilmicosin, erythromycin ethylsuccinate and clindamycin by CE with electrochemiluminescence detection using azithromycin as internal standard and its applications.

A sensitive approach for the simultaneous determination of tilmicosin, erythromycin ethylsuccinate and clindamycin was developed by CE coupled with electrochemiluminescence detection with ionic liquid. The parameters for CE, electrochemiluminescence detection and the effect of ionic liquid were investigated systematically. The three analytes were well separated and detected within 8 min. The limits of detection (S/N=3) of tilmicosin, erythromycin ethylsuccinate and clindamycin are 3.4x10(-9), 2.3x10(-8) and 1.3x10(-8) mol/L, respectively. The precisions (RSD%) of the peak area and the migration time are from 0.8 to 1.5% and from 0.2 to 0.5% within a day and from 1.8 to 2.7% and from 0.6 to 0.8% in 3 days, respectively. The limits of quantitation (S/N=10) of tilmicosin, erythromycin ethylsuccinate and clindamycin are 3.2x10(-8), 2.9x10(-7) and 9.1x10(-8) mol/L in human urines and 5.5x10(-8), 3.2x10(-7) and 2.1x10(-7) mol/L in milk samples, respectively. The recoveries of three analytes at different concentration levels in urine, milk and drugs are between 90.0 and 104.7%. The proposed method was successfully applied to the determination of three analytes in human urine, milk and drugs.

[Specific ototoxic effects of monomycin in immature animals].

Dynamics of the hearing function was evaluated using immature animals based on the SSCP data. Morphological characteristics of the cochlear auditory ganglion were studied after administration of therapeutic doses of the ototoxic antibiotic monomycin. Untreated animals served as controls. The results of morphofunctional investigations were evaluated in comparison with the similar data obtained in adult cats after injection of the same doses of monomycin.

Multiple aphthoid syphilitic chancres of the oral cavity.

We describe the case of a 31-year-old man who was affected by three asymptomatic, aphthoid, syphilitic chancres of the oral cavity. These lesions were accompanied by right latero-cervical and chin lymphadenopathy. The infection was previously diagnosed as aphthous stomatitis. The search for Treponema pallidum by means of darkfield microscope examination was positive. The patient was successfully treated with oral erythromycin ethylsuccinate. To our knowledge, this is the first case of multiple aphthoid syphilitic chancres of the oral cavity reported in the literature. We suggest that all patients with a recent history of painless ulcers in the oral cavity, accompanied by regional lymphadenopathy in which the clinical diagnosis has not been confirmed, should undergo a darkfield microscope examination.

Pharmacokinetics of erythromycin after the administration of intravenous and various oral dosage forms to dogs.

The purpose of this study was to describe and compare the pharmacokinetic properties of different formulations of erythromycin in dogs. Erythromycin was administered as lactobionate (10 mg/kg, IV), estolate tablets (25 mg/kg p.o.) and ethylsuccinate tablets or suspension (20 mg/kg p.o.). After intravenous (i.v.) administration, the principal pharmacokinetic parameters were (mean +/- SD): AUC((0-infinity)) 4.20 +/- 1.66 microg x h/mL; C(max) 6.64 +/- 1.38 microg/mL; V(z) 4.80 +/- 0.91 L/kg; Cl(t) 2.64 +/- 0.84 L/h.kg; t((1/2)lambda) 1.35 +/- 0.40 h and MRT 1.50 +/- 0.47 h. After the administration of estolate tablets and ethylsuccinate suspension, the principal pharmacokinetic parameters were (mean +/- SD): C(max), 0.30 +/- 0.17 and 0.17 +/- 0.09 microg/mL; t(max), 1.75 +/- 0.76 and 0.69 +/- 0.30 h; t((1/2)lambda), 2.92 +/- 0.79 and 1.53 +/- 1.28 h and MRT, 5.10 +/- 1.12 and 2.56 +/- 1.77 h, respectively. The administration of erythromycin ethylsuccinate tablets did not produce measurable serum concentrations. Only the i.v. administration rendered serum concentrations above MIC(90) = 0.5 microg/mL for 2 h. However, these results should be cautiously interpreted as tissue erythromycin concentrations have not been measured in this study and, it is recognized that they can reach much higher concentrations than in blood, correlating better with clinical efficacy.

Impact of Long-Term Erythromycin Therapy on the Oropharyngeal Microbiome and Resistance Gene Reservoir in Non-Cystic Fibrosis Bronchiectasis.

Long-term macrolide therapy reduces rates of pulmonary exacerbation in bronchiectasis. However, little is known about the potential for macrolide therapy to alter the composition and function of the oropharyngeal commensal microbiota or to increase the carriage of transmissible antimicrobial resistance. We assessed the effect of long-term erythromycin on oropharyngeal microbiota composition and the carriage of transmissible macrolide resistance genes in 84 adults with bronchiectasis, enrolled in the Bronchiectasis and Low-dose Erythromycin Study (BLESS) 48-week placebo-controlled trial of twice-daily erythromycin ethylsuccinate (400 mg). Oropharyngeal microbiota composition and macrolide resistance gene carriage were determined by 16S rRNA gene amplicon sequencing and quantitative PCR, respectively. Long-term erythromycin treatment was associated with a significant increase in the relative abundance of oropharyngeal Haemophilus parainfluenzae (P = 0.041) and with significant decreases in the relative abundances of Streptococcus pseudopneumoniae (P = 0.024) and Actinomyces odontolyticus (P = 0.027). Validation of the sequencing results by quantitative PCR confirmed a significant decrease in the abundance of Actinomyces spp. (P = 0.046). Erythromycin treatment did not result in a significant increase in the number of subjects who carried erm(A), erm(B), erm(C), erm(F), mef(A/E), and msrA macrolide resistance genes. However, the abundance of erm(B) and mef(A/E) gene copies within carriers who had received erythromycin increased significantly (P < 0.05). Our findings indicate that changes in oropharyngeal microbiota composition resulting from long-term erythromycin treatment are modest and are limited to a discrete group of taxa. Associated increases in levels of transmissible antibiotic resistance genes within the oropharyngeal microbiota highlight the potential for this microbial system to act as a reservoir for resistance.IMPORTANCE Recent demonstrations that long-term macrolide therapy can prevent exacerbations in chronic airways diseases have led to a dramatic increase in their use. However, little is known about the wider, potentially adverse impacts of these treatments. Substantial disruption of the upper airway commensal microbiota might reduce its contribution to host defense and local immune regulation, while increases in macrolide resistance carriage would represent a serious public health concern. Using samples from a randomized controlled trial, we show that low-dose erythromycin given over 48 weeks influences the composition of the oropharyngeal commensal microbiota. We report that macrolide therapy is associated with significant changes in the relative abundances of members of the Actinomyces genus and with significant increases in the carriage of transmissible macrolide resistance. Determining the clinical significance of these changes, relative to treatment benefit, now represents a research priority.

Antibiotics for whooping cough (pertussis).

BACKGROUND: Whooping cough is a highly contagious disease. Infants are at highest risk of severe disease and death. Erythromycin for 14 days is currently recommended for treatment and contact prophylaxis, but is of uncertain benefit. OBJECTIVES: To study the benefits and risks of antibiotic treatment of and contact prophylaxis against whooping cough. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), the Database of Abstracts of Reviews of Effects (DARE) (The Cochrane Library Issue 1, 2007); MEDLINE (January 1966 to March 2007); EMBASE (January 1974 to March 2007). SELECTION CRITERIA: All randomised and quasi-randomised controlled trials of antibiotics for treatment of, and contact prophylaxis against, whooping cough. DATA COLLECTION AND ANALYSIS: Three to four review authors independently extracted data and assessed the quality of each trial. MAIN RESULTS: Thirteen trials with 2197 participants met the inclusion criteria: 11 trials investigated treatment regimens; 2 investigated prophylaxis regimens. The quality of the trials was variable.Short-term antibiotics (azithromycin for three to five days, or clarithromycin or erythromycin for seven days) were as effective as long-term (erythromycin for 10 to 14 days) in eradicating Bordetella pertussis (B. pertussis) from the nasopharynx (relative risk (RR) 1.02, 95% confidence interval (CI) 0.98 to 1.05), but had fewer side effects (RR 0.66, 95% CI 0.52 to 0.83). Trimethoprim/sulfamethoxazole for seven days was also effective. Nor were there differences in clinical outcomes or microbiological relapse between short and long-term antibiotics. Contact prophylaxis of contacts older than six months of age with antibiotics did not significantly improve clinical symptoms or the number of cases developing culture-positive B. pertussis. AUTHORS' CONCLUSIONS: Although antibiotics were effective in eliminating B. pertussis, they did not alter the subsequent clinical course of the illness. There is insufficient evidence to determine the benefit of prophylactic treatment of pertussis contacts.

Nondestructive quantitative analysis of erythromycin ethylsuccinate powder drug via short-wave near-infrared spectroscopy combined with radial basis function neural networks.

A new assay method for the nondestructive determination of erythromycin ethylsuccinate powder drug via short-wave near-infrared spectroscopy (NIR) combined with radial basis function (RBF) neural networks is investigated. The modern near-infrared spectroscopy analysis technique is efficient, simple and nondestructive, which has been used in chemical analysis in diverse fields. Short-wave NIR is a more rapid, flexible, and cost-effective method to control product concentration in pharmaceutical industry. The RBF neural networks are local approximation networks that have superiorities in function approximation and learning speed. In addition, the structure of RBF networks is simple. Estimate and calibration of the sample concentration via short-wave NIR are made with the aid of RBF models based on conventional spectra, standard normal variate (SNV), multiplicative scatter correction (MSC) and the first-derivative spectra. Various optimum models of them are established and compared. Experiment results show that the models of SNV spectra can give better performance, and the optimized RBF neural network model after SNV treatment were given, by which the root-mean-square-errors (RMSE) for calibration set and test set were 0.3266% and 0.5244%, respectively and the correlation coefficients (R) for calibration set and test set were 0.9942 and 0.9852, respectively. The proposed RBF method based on short-wave NIR is more valuable and economical for quantitative analysis than traditional methods such as partial least squares (PLS).

Simultaneous determination of erythromycin ethylsuccinate and its metabolite erythromycin in human plasma using liquid chromatography-electrospray ionization mass spectrometry for clinical study.

A sensitive and selective liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) method was developed for simultaneous identification and quantification of erythromycin ethylsuccinate and erythromycin in human plasma, which can be well applied to clinical study. The method was based on liquid-liquid extraction, followed by a LC procedure with an ODS C18 column, and mixture of acetonitrile and 1.67 mmol/l acetic acid as mobile phase. MS detection was performed using a single quadrupole mass spectrometer in positive selected ion monitoring (SIM) mode. The method was validated to be linear, precise and accurate. The lower limit of quantification of erythromycin ethylsuccinate and erythromycin were both 0.5 ng/ml. The proposed method enables the unambiguous identification and quantification of erythromycin ethylsuccinate and erythromycin for clinical drug monitoring.

Construction of universal quantitative models for determination of roxithromycin and erythromycin ethylsuccinate in tablets from different manufacturers using near infrared reflectance spectroscopy.

Universal quantitative models using NIR reflectance spectroscopy were developed for the analysis of API contents (active pharmaceutical ingredient) in roxithromycin and erythromycin ethylsuccinate tablets from different manufacturers in China. The two quantitative models were built from 78 batches of roxithromycin samples from 18 different manufacturers with the API content range from 19.5% to 73.9%, and 66 batches erythromycin ethylsuccinate tablets from 36 manufacturers with the API content range from 28.1% to 70.9%. Three different spectrometers were used for model construction in order to have robust and universal models. The root mean square errors of cross validation (RMSECV) and the root mean square errors of prediction (RMSEP) of the model for roxithromycin tablets were 1.84% and 1.45%, respectively. The values of RMSECV and RMSEP of the model for erythromycin ethylsuccinate tablets were 2.31% and 2.16%, respectively. Based on the ICH guidelines and characteristics of NIR spectroscopy, the quantitative models were then evaluated in terms of specificity, linearity, accuracy, precision, robustness and model transferability. Our study has shown that it is feasible to build a universal quantitative model for quick analysis of pharmaceutical products from different manufacturers. Therefore, the NIR method could be used as an effective method for quick, non-destructive inspection of medicines in the distribution channels or open market.

A validated spectrofluorometric assay for the determination of certain macrolide antibiotics in pharmaceutical formulations and spiked biological fluids.

This paper describes a simple spectrofluorometric method for the analysis of 4 macrolide antibiotics. The method is based on the condensation of 10% (w/v) malonic acid and acetic acid anhydride under the catalytic effect of tertiary amine groups of the studied macrolides. The relative fluorescence intensity of the condensation product was measured at 397/452 nm (excitation/emission) for azithromycin dihydrate and at 392/445 nm (for clarithromycin, erythromycin ethylsuccinate, and roxithromycin. All variables affecting the reaction conditions were studied. The effects of potential interference due to common excipients, such as starch, lactose, sucrose, glucose, gum acacia, and magnesium stearate, as well as trimethoprim and sulfisoxazole acetyl formulated in primomycin capsules and pediazole oral suspension, respectively, were studied. A validation study for the proposed method was carried out according to U.S. Pharmacopeia 2002. The linearity ranges were 3-80 ng/mL for all of the cited macrolides. The limit of detection range was 0.74-1.20 ng/mL, while the limit of quantitation range was 2.47-4.02 ng/mL. The method was applied for the assay of the studied macrolides in pure pharmaceutical formulations and in spiked biological fluids. Results were compared with those obtained from the reported method, where calculated t- and F-values indicated high accuracy and good precision for the proposed method.

Antibiotics for whooping cough (pertussis).

BACKGROUND: Whooping cough is a highly contagious disease. Infants are the population at highest risk of severe disease and death. Erythromycin for 14 days is recommended for treatment and contact prophylaxis but this regime is considered inconvenient and prolonged. The value of contact prophylaxis is uncertain. OBJECTIVES: To study the benefits and risks of antibiotic treatment of and contact prophylaxis against whooping cough. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2004); MEDLINE (January 1966 to February 2004); EMBASE (January 1974 to August 2003); conference abstracts and reference lists of articles were searched. Study investigators and pharmaceutical companies were approached for additional information (published or unpublished studies). There were no constraints based on language or publication status. SELECTION CRITERIA: All randomised and quasi-randomised controlled trials of antibiotics for treatment of and contact prophylaxis against whooping cough were included in the systematic review. DATA COLLECTION AND ANALYSIS: At least three reviewers independently extracted data and assessed the quality of each trial. MAIN RESULTS: Twelve trials with 1,720 participants met the inclusion criteria. Ten trials investigated treatment regimens and two investigated prophylaxis regimens. The quality of the trials was variable. Results showed that short-term antibiotics (azithromycin for three days, clarithromycin for seven days, or erythromycin estolate for seven days) were equally effective with long-term antibiotic treatment (erythromycin estolate or erythromycin for 14 days) in the microbiological eradication of Bordetella pertussis (B. pertussis) from the nasopharynx. The relative risk (RR) was 1.02 (95% confidence interval (CI) 0.98 to 1.05). Side effects were fewer with short-term treatment (RR 0.66; 95% CI 0.52 to 0.83). There were no differences in clinical improvement or microbiological relapse between short and long-term treatment regimens. Contact prophylaxis (of contacts older than six months of age) with antibiotics did not significantly improve clinical symptoms or the number of cases that developed culture positive B. pertussis. AUTHORS' CONCLUSIONS: Antibiotics are effective in eliminating B. pertussis from patients with the disease, rendering them non-infectious, but do not alter the subsequent clinical course of the illness. Effective regimens include: three days of azithromycin, seven days of clarithromycin, seven or 14 days of erythromycin estolate, and 14 days of erythromycin ethylsuccinate. Considering microbiological clearance and side effects, three days of azithromycin or seven days of clarithromycin are the best regimens. Seven days of trimethoprim/sulfamethoxazole also appeared to be effective for the eradication of B. pertussis from the nasopharynx and may serve as an alternative antibiotic treatment for patients who cannot tolerate a macrolide. There is insufficient evidence to determine the benefit of prophylactic treatment of pertussis contacts.

Cholestatic hepatitis from erythromycin ethylsuccinate. Report of two cases.

Cholestatic hepatitis developed in two patients while they were receiving erythromycin ethylsuccinate. Both patients had received the drug without apparent problem within two months of the episode of drug-related cholestatic injury. In both, there was complete resolution of the hepatic injury upon withdrawal of the drug. Erythromycin ethylsuccinate should be added to the list of drugs causing cholestatic hepatitis.

Comparison of erythromycin estolate and erythromycin ethylsuccinate for treatment of pertussis. The Erythromycin Study Group.

In an open randomized multicenter study 190 culture-positive pediatric ambulatory pertussis patients were treated for 14 days with either erythromycin estolate (EST) (n = 93; 40 mg/kg/day divided in 2 doses) or erythromycin ethylsuccinate (ETH) (n = 97; 60 mg/kg/day divided in 3 doses). On day 14 Bordetella pertussis was recovered from cultures of 2 patients (2.2%) treated with EST and 1 patient (1.0%) treated with ETH. Despite the fact that 151 patients (79.4%) had reached the early paroxysmal stage at initiation of antimicrobial therapy, clinical improvement was seen in the majority (reduced frequency and severity of coughing: EST, 77.4 and 67.7%; ETH, 74.2 and 63.9%, respectively). Drug-related side effects were noted in 11 patients (11.8%) treated with EST and 16 patients (16.5%) treated with ETH (P greater than 0.05) and consisted mainly of minor gastrointestinal complaints. Erythromycin estolate in a lower dose administered only twice a day was equivalent to erythromycin ethylsuccinate in all aspects and proved to be adequate antimicrobial treatment for pertussis patients.

Mycoplasma pneumoniae and Chlamydia pneumoniae in pediatric community-acquired pneumonia: comparative efficacy and safety of clarithromycin vs. erythromycin ethylsuccinate.

We evaluated 260 previously healthy children ages 3 through 12 years who had clinical signs and symptoms of pneumonia, radiographically confirmed. Patients were randomized 1:1 to a 10-day course of either clarithromycin suspension 15 mg/kg/day divided twice a day or erythromycin suspension 40 mg/kg/day divided twice a day or three times a day. Evidence of infection with Chlamydia pneumoniae was detected in 28% (74) of patients: 13% (34) by nasopharyngeal culture and 18% (48) by serology with the microimmunofluorescence assay. Evidence of infection with Mycoplasma pneumoniae was detected in 27% (69) of patients: 20% (53) by nasopharyngeal culture or polymerase chain reaction and 17% (44) by serology with the use of enzyme-linked immunosorbent assay. Serologic confirmation of infection was observed in 23% (8) and 53% (28) of patients with bacteriologically detected C. pneumoniae and M. pneumoniae, respectively. Treatment with clarithromycin vs. erythromycin, respectively, yielded the following outcomes: clinical success 98% (121 of 124) vs. 95% (105 of 110); radiologic success 98% (109 of 111) vs. 94% (92 of 110); and eradication by pathogen, C. pneumoniae 79% (15 of 19) vs. 86% (12 of 14) and M. pneumoniae 100% (9 of 9) vs. 100% (4 of 4). Adverse events were primarily gastrointestinal occurring in almost one-fourth of patients in both groups, and were mild to moderate in severity. Clarithromycin and erythromycin were similarly effective and safe for the treatment of radiographically proved, community-acquired pneumonia in children older than 2 years old.(ABSTRACT TRUNCATED AT 250 WORDS)

Randomized, double blind comparison of brand and generic antibiotic suspensions: I. A study of taste in adults.

BACKGROUND: A belief that brand oral liquid medications taste better than their generic counterparts may influence prescribing habits among pediatricians. METHODS: We undertook a prospective, randomized, double blinded, comparative evaluation of the taste of brand and generic erythromycin ethylsuccinate, cephalexin monohydrate, erythromycin ethylsuccinate/sulfisoxazole, penicillin V potassium and trimethoprim-sulfamethoxazole in 42 adult volunteers. Subjects tasted one class of brand and generic antibiotics and rated them according to smell, texture, taste and aftertaste. RESULTS: At least one generic preparation of cephalexin, erythromycin ethylsuccinate/sulfisoxazole and penicillin V potassium was rated equal in taste to the respective brand name products. However, brand erythromycin estolate and trimethoprim-sulfamethoxazole name brand suspensions rated significantly higher than the other products tested. CONCLUSIONS: Based on our results brand name oral antibiotic formulations do not necessarily taste better than their generic counterparts.

Treatment of neonatal conjunctivitis.

The effect of different treatment regimens on clinical and microbiologic cures of neonatal conjunctivitis was evaluated during a 32-day observation period. In 84 infants with mild to moderate conjunctivitis and no signs of dacryocystitis, clinical cures were achieved in more than 50% of the cases with lid hygiene only. Staphylococcus aureus was the most common organism (48%) isolated from these infants. Chlamydia trachomatis could not be isolated from eyes with mild to moderate conjunctivitis. Forty-four infants with severe conjunctivitis, with or without dacryocystitis, were randomly assigned to treatment with either topical chloramphenicol or oral erythromycin for 14 days. Chlamydia trachomatis was isolated from 19 (43%) of these infants. All infants with chlamydial conjunctivitis who were treated with 25 mg/kg of oral erythromycin ethylsuccinate twice daily for 14 days were clinically and microbiologically cured. In contrast, all treatment of chlamydial conjunctivitis with topical chloramphenicol failed clinically as well as microbiologically. Dacryocystitis was a common complication in neonatal conjunctivitis (17%). The clinical failures in neonatal nonchlamydial conjunctivitis were associated with persistent obstruction of the nasolacrimal duct.