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PubMed2001

BMS-284756 (T-3811ME) a new fluoroquinolone: in vitro activity against Legionella, efficacy in a guinea pig model of L. pneumophila pneumonia and pharmacokinetics in guinea pigs.

The activity of BMS-284756 was studied against extracellular Legionella spp. and intracellular Legionella pneumophila, and for the treatment of guinea pigs with L. pneumophila pneumonia. The BMS-284756 MIC(50) of 22 different Legionella spp. strains was 0.008 mg/L, compared with 0.016 and 0.125 mg/L for levofloxacin and azithromycin, respectively. BMS-284756 (1 mg/L) reduced the intracellular concentrations of two L. pneumophila strains grown in guinea pig alveolar macrophages by c. 1.5 log(10 )cfu/mL, and was more active than erythromycin, but less active than azithromycin or levofloxacin at the same drug concentrations. Efficacy studies of BMS-284756, levofloxacin and azithromycin were performed in guinea pigs with L. pneumophila pneumonia. In infected guinea pigs given BMS-284756 10 mg/kg ip, mean peak plasma levels were 1.8 mg/L at 0.5 h and 0.7 mg/L at 1 h post-dose. The elimination half-life in plasma was 0.5 h, and the AUC(0-24 )was 1.7 mg*h/L, about 2% of the AUC(0-24 )for a single 400 mg oral dose in man. Sixteen of 18 L. pneumophila-infected guinea pigs treated with BMS-284756 10 mg/kg ip once daily for 5 days survived for 7 days post-antimicrobial therapy, as did 11 of 12 guinea pigs treated with azithromycin 15 mg/kg ip once daily for 2 days. All 12 animals that were treated with levofloxacin 10 mg/kg ip once daily for 5 days survived. None of 12 control animals treated with saline survived. Animals treated with BMS-284756 had significantly higher residual lung counts of L. pneumophila at the end of therapy than did animals treated with levofloxacin or azithromycin, which may be attributable to the very low drug concentrations that were obtained. BMS-284756 was more active than erythromycin against L. pneumophila in infected macrophages, and effectively treated animals with experimental L. pneumophila pneumonia. These data support further studies of BMS-284756 for the treatment of Legionnaires' disease.

Animals↗

PubMed1997

Comparative study of bactericidal activities, postantibiotic effects, and effects of bacterial virulence of penicillin G and six macrolides against Streptococcus pneumoniae.

In this report, we present MIC, bactericidal activity, postantibiotic effect (PAE), and in vivo infectivity data for postantibiotic-phase pneumococci. We compared and evaluated penicillin G and six macrolides, erythromycin, azithromycin, clarithromycin, dirithromycin, roxithromycin, and spiramycin, against 10 strains of pneumococci with various levels of susceptibility to penicillin. All of the agents, except azithromycin, exhibited a bactericidal effect (a > or = 3 log10 decrease in the number of CFU per milliliter) after 4 h of exposure to a concentration equal to 10 times the MIC, displaying the following hierarchy: spiramycin = penicillin G = erythromycin = dirithromycin = clarithromycin = roxithromycin > azithromycin. The bactericidal rate of penicillin G was significantly lower for resistant strains (MIC, > or = 2 microg/ml), while bactericidal rates of macrolides were unaffected by penicillin susceptibility. A PAE was induced in all of the strains by all of the antibiotics after exposure for 1 h to a concentration equivalent to 10 times the MIC. The mean duration of PAEs varied between 2.3 and 3.9 h, showing the following hierarchy: spiramycin = dirithromycin = clarithromycin = erythromycin = roxithromycin > azithromycin > penicillin G. Virulence studies were performed with immunocompetent mice by intraperitoneal inoculation of virulent, penicillin-susceptible serotype 3 pneumococci which had been pre-exposed to penicillin G or a macrolide for 1 h. A significant decrease in the virulence of postantibiotic-phase pneumococci was induced only by erythromycin, azithromycin, dirithromycin, and spiramycin, displaying 5.9-, 7.1-, 4.2-, and 3.6-fold increases in the 50% lethal dose (LD50) compared to a control suspension, respectively. No significant correlation could be demonstrated between the LD50 and the MIC, bactericidal activity, or PAE duration. These results suggest that antimicrobial interaction with host defenses in terms of virulence might be a significant parameter that could influence the drug or drug regimen of choice.

Animals↗

PubMed2000

Activities and postantibiotic effects of gemifloxacin compared to those of 11 other agents against Haemophilus influenzae and Moraxella catarrhalis.

The activity of gemifloxacin against Haemophilus influenzae and Moraxella catarrhalis was compared to those of 11 other agents. All quinolones were very active (MICs, </=0.125 microgram/ml) against 248 quinolone-susceptible H. influenzae isolates (40.7% of which were beta-lactamase positive); cefixime (MICs, </=0.125 microgram/ml) and amoxicillin-clavulanate (MICs </=4.0 microgram/ml) were active, followed by cefuroxime (MICs, </=16.0 microgram/ml); azithromycin MICs were </=4.0 microg/ml. For nine H. influenzae isolates with reduced quinolone susceptibilities, the MICs at which 50% of isolates are inhibited (MIC(50)s) were 0.25 microgram/ml for gemifloxacin and 1.0 microgram/ml for the other quinolones tested. All strains had mutations in GyrA (Ser84, Asp88); most also had mutations in ParC (Asp83, Ser84, Glu88) and ParE (Asp420, Ser458), and only one had a mutation in GyrB (Gln468). All quinolones tested were equally active (MICs, </=0.06 microgram/ml) against 50 M. catarrhalis strains; amoxicillin-clavulanate, cefixime, cefuroxime, and azithromycin were very active. Against 10 H. influenzae strains gemifloxacin, levofloxacin, sparfloxacin, and trovafloxacin at 2x the MIC and ciprofloxacin at 4x the MIC were uniformly bactericidal after 24 h, and against 9 of 10 strains grepafloxacin at 2x the MIC was bactericidal after 24 h. After 24 h bactericidal activity was seen with amoxicillin-clavulanate at 2x the MIC for all strains, cefixime at 2x the MIC for 9 of 10 strains, cefuroxime at 4x the MIC for all strains, and azithromycin at 2x the MIC for all strains. All quinolones except grepafloxacin (which was bactericidal against four of five strains) and all ss-lactams at 2x to 4x the MIC were bactericidal against five M. catarrhalis strains after 24 h; azithromycin at the MIC was bactericidal against all strains after 24 h. The postantibiotic effects (PAEs) against four quinolone-susceptible H. influenzae strains were as follows: gemifloxacin, 0.3 to 2.3 h; ciprofloxacin, 1.3 to 4.2 h; levofloxacin, 2.8 to 6.2 h; sparfloxacin, 0.6 to 3.0 h; grepafloxacin, 0 to 2.1 h; trovafloxacin, 0.8 to 2.8 h. At 10x the MIC, no quinolone PAEs were found against the strain for which quinolone MICs were increased. Azithromycin PAEs were 3.7 to 7.3 h.

Anti-Bacterial Agents↗

PubMed2002

Synergistic activities of macrolide antibiotics against Pseudomonas aeruginosa, Burkholderia cepacia, Stenotrophomonas maltophilia, and Alcaligenes xylosoxidans isolated from patients with cystic fibrosis.

Azithromycin and clarithromycin were paired with other antibiotics to test synergistic activity against 300 multidrug-resistant pathogens isolated from cystic fibrosis (CF) patients. Clarithromycin-tobramycin was most active against Pseudomonas aeruginosa and inhibited 58% of strains. Azithromycin-trimethoprim-sulfamethoxazole, azithromycin-ceftazidime, and azithromycin-doxycycline or azithromycin-trimethoprim-sulfamethoxazole inhibited 40, 20, and 22% of Stenotrophomonas maltophilia, Burkholderia cepacia complex, and Achromobacter (Alcaligenes) xylosoxidans strains, respectively.

Alcaligenes↗

PubMed2006

Mycoplasma genitalium: a common cause of persistent urethritis among men treated with doxycycline.

BACKGROUND/OBJECTIVE: Persistent or recurrent non-gonococcal urethritis (NGU) is commonly observed in men attending sexually transmitted diseases clinics. The aim of this study was to determine the importance of Mycoplasma genitalium in this condition and to monitor the effect of treatment with macrolides. METHODS: 78 male patients with persistent or recurrent symptomatic non-chlamydial NGU after treatment with doxycycline 200 mg day 1 and 100 mg for the following 8 days were enrolled. The patients had a first void urine specimen examined for the presence of M genitalium DNA by an inhibitor controlled PCR. Treatment with azithromycin and/or erythromycin and/or repeat doxycycline was prescribed at the doctor's discretion to the M genitalium positive men. Microbiological cure rate was determined at a 3 week follow up visit. RESULTS: M genitalium was detected in 32 (41%) men and those infected had more often a high grade urethritis (>10 PMNLs/hpf) than those negative for M genitalium (p = 0.01). 22 men had been treated with azithromycin, 19 of whom received 1.5 g over 5 days and three received 1 g as a single dose. All 20 who came back after treatment were M genitalium negative. Only two of five erythromycin treated controlled cases were M genitalium negative after treatment compared to all six given azithromycin at inclusion (p = 0.12). Six of nine female partners were M genitalium positive; they were treated with 1.5 g azithromycin given over 5 days, and the four tested were M genitalium negative after treatment. CONCLUSIONS: M genitalium is a common cause of persistent or recurrent urethritis among men treated with doxycycline and erythromycin appears to be less efficient than azithromycin in eradicating the infection.

Adult↗

PubMed2005

Patient stratification in the management of acute bacterial exacerbation of chronic bronchitis: the role of levofloxacin 750 mg.

This is the first prospective clinical trial in which patients with acute bacterial exacerbation of chronic bronchitis have been stratified by degree of underlying illness. Uncomplicated patients were randomised to levofloxacin 750 mg once daily (q.d.) for 3 days or azithromycin q.d. for 5 days. Complicated patients were randomised to levofloxacin 750 mg q.d. for 5 days or amoxicillin 875 mg/clavulanate 125 mg twice daily for 10 days. Regardless of therapy, complicated patients demonstrated lower clinical and microbiological success than uncomplicated patients. Clinical success for clinically evaluable patients was similar for levofloxacin and azithromycin (93.0 versus 90.1%, respectively), and levofloxacin and amoxicillin/clavulanate (79.2 versus 81.7%, respectively). For microbiologically evaluable patients, clinical response to levofloxacin for 3 days was superior to azithromycin for 5 days (96.3 versus 87.4%, respectively), and levofloxacin for 5 days was similar to amoxicillin/clavulanate for 10 days (81.4 versus 80.9%, respectively). Microbiological eradication was superior for levofloxacin for 3 days compared with azithromycin for 5 days (93.8 versus 82.8%, respectively), and similar for levofloxacin and amoxicillin/clavulanate for 10 days (81.4 versus 79.8%, respectively). In conclusion, levofloxacin 750 mg for 3 days was comparable to azithromycin for 5 days for uncomplicated patients with acute bacterial exacerbation of chronic bronchitis, while 5 days of 750 mg levofloxacin was comparable to 10 days of amoxicillin/clavulanate for complicated acute bacterial exacerbation of chronic bronchitis.

Administration, Oral↗

PubMedDate not supplied

The Viriato Study: update of antimicrobial susceptibility data of bacterial pathogens from community-acquired respiratory tract infections in Portugal in 2003 and 2004.

The Viriato Study is a nationwide, prospective, multicenter surveillance study of the antimicrobial susceptibility of bacterial pathogens commonly associated with community-acquired respiratory tract infections in Portugal. In 2003 and 2004 a total of 2945 isolates was recovered in the 29 laboratories that participated in the study. Testing was undertaken in a central laboratory. Of the 513 Streptococcus pyogenes strains isolated from patients with acute tonsillitis all were susceptible to penicillin and other beta-lactams but 18.9% were resistant to erythromycin, clarithromycin and azithromycin. The M phenotype dominated (67%), conferring resistance to erythromycin (MIC90 = 16 mg/L), clarythromycin and azithromycin, but susceptibility to clindamycin (MIC90 = 0.094 mg/L). From patients with lower respiratory tract infection 1,300 strains of Streptococcus pneumoniae, 829 of Haemophilus influenzae, and 303 of Moraxella catarrhalis were studied. Among S. pneumoniae isolates 18.4% were resistant to penicillin (3.5% showing high-level resistance), 7.1% to cefuroxime, 0.5% to amoxicillin and amoxicillin/clavulanate, 18.8% to erythromycin, clarithromycin and azithromycin, 14.9% to tetracycline, 16.5% to co-trimoxazole, and 0.4% to levofloxacin. Beta-lactamases were produced by 10.0% of H. influenzae and 96.4% of M. catarrhalis. In H. influenzae resistance to clarithromycin was 5.5% and to co-trimoxazole was 13.4%. Most strains were susceptible to amoxicillin/clavulanate, cefuroxime, azithromycin, tetracycline and ciprofloxacin. In M. catarrhalis resistance to co-trimoxazole was 27.1% and to tetracycline 1.0%. All strains were susceptible to amoxicillin/clavulanate, cefuroxime, clarithromycin, azithromycin and ciprofloxacin. Penicillin was the most active antimicrobial agent against S. pyogenes and amoxycillin/clavulanate and the quinolones the most active in vitro simultaneously against S. pneumoniae, H. influenza and M. catarrhalis.

Anti-Bacterial Agents↗

PubMed2004

Real-time imaging of drug-membrane interactions by atomic force microscopy.

Understanding drug-biomembrane interactions at high resolution is a key issue in current biophysical and pharmaceutical research. Here we used real-time atomic force microscopy (AFM) imaging to visualize the interaction of the antibiotic azithromycin with lipid domains in model biomembranes. Various supported lipid bilayers were prepared by fusion of unilamellar vesicles on mica and imaged in buffer solution. Phase-separation was observed in the form of domains made of dipalmitoylphosphatidylcholine (DPPC), sphingomyelin (SM), or SM/cholesterol (SM/Chl) surrounded by a fluid matrix of dioleoylphosphatidylcholine (DOPC). Time-lapse images collected following addition of 1 mM azithromycin revealed progressive erosion and disappearance of DPPC gel domains within 60 min. We attribute this effect to the disruption of the tight molecular packing of the DPPC molecules by the drug, in agreement with earlier biophysical experiments. By contrast, SM and SM-Chl domains were not modified by azithromycin. We suggest that the higher membrane stability of SM-containing domains results from stronger intermolecular interactions between SM molecules. This work provides direct evidence that the perturbation of lipid domains by azithromycin strongly depends on the lipid nature and opens the door for developing new applications in membrane biophysics and pharmacology.

Androstanes↗

PubMed2005

Effect of cirrhosis on antibiotic efficacy in a rat model of pneumococcal pneumonia.

A rat model was used to study the effects of cirrhosis on antibiotic therapy of pneumococcal pneumonia. Cirrhotic and control male Sprague-Dawley rats were infected transtracheally with type 3 Streptococcus pneumoniae. Treatment began 18 h later with phosphate-buffered saline (PBS), azithromycin (50 mg/kg), trovafloxacin (50 mg/kg), or ceftriaxone (100 mg/kg) injected subcutaneously twice daily for 5 days. Antibiotic concentrations were measured by high-performance liquid chromatography. Azithromycin, trovafloxacin, and ceftriaxone were all equally effective at preventing mortality in both cirrhotic and normal rats. Free fraction area under the curve to minimum inhibitory concentration ratio (AUC/MIC) and maximum calculated serum concentration to MIC ratio (C(max)/MIC) and percent time that the serum concentration exceeded the MIC (%T > MIC) were greater for ceftriaxone compared with azithromycin or trovafloxacin. Azithromycin achieved higher concentrations in bronchoalveolar lavage fluid (BALF), epithelial lining fluid (ELF), and BAL white blood cells than ceftriaxone or trovafloxacin in cirrhotic rats. Macrolide, beta-lactam, or fluoroquinolone antibiotic efficacy in a pneumococcal pneumonia model does not appear to be affected by hepatic cirrhosis.

Animals↗

PubMed2006

Micronucleus frequency in women with genital Chlamydia Trachomatis infection before and after therapy.

The main aim of the present study was to investigate the influence of infection with the intracellular bacterium Chlamydia trachomatis, and subsequent treatments with oral doxycycline or azithromycin on the frequency of micronuclei (MN) in peripheral blood lymphocytes of adult female patients receiving standard doses of these drugs. The frequency of micronuclei was measured in the lymphocytes of 38 newly diagnosed adult women with genital C. trachomatis infection. Samples were taken before and after the therapy, and from 50 healthy control females. The therapy was taken orally during 10 days at 2 x 100 mg per day, and then for another 10 days at 1 x 100 mg per day for doxycycline, and as a single dose of 1g for azithromycin. Isolated lymphocytes from all subjects were cultured by use of the whole-blood method and blocked in metaphase with cytochalasin B (Cyt B). One thousand binucleate cells per subject were scored according to published criteria. The frequency of micronuclei was not significantly higher in samples of infected females before therapy, compared with the baseline frequency in healthy control females (p > 0.05). In patients who received doxycycline, the micronucleus frequency after the end of therapy was significantly higher than before treatment (p < 0.001). The mean frequency of micronuclei in females after the end of the therapy with azithromycin did not show an increase (p > 0.05). The application of linear regression analysis showed that the difference in micronucleus frequency before and after therapy (effect of the antibiotics) was affected by the therapy type. Age and smoking did not affect micronucleus frequency in analyzed samples of patients (p = 0.078, 0.579). We conclude that C. trachomatis infection does not induce micronuclei in peripheral blood lymphocytes of infected adult female patients. Therapy with doxycycline significantly increases the micronucleus frequency in lymphocytes of treated patients, but treatment with azithromycin does not induce micronuclei.

Adult↗

PubMed2004

[An example of simulation for a better understanding of PK/PD relationship of antibiotics].

The interpretation of PK/PD indices is specific to each class of antibiotics. In order to illustrate this, we developed a multidisciplinary tutorial program based on simulation of clinical cases. Three drugs were included in this software: tobramycin, vancomycin and azithromycin. From the dosage regimen proposed by the user, the model simulates a plotting of antibiotic plasma concentrations vs. time (tobramycin, vancomycin and azithromycin) and tissue concentrations (azithromycin). Peak and trough concentrations are calculated at steady-state. A commentary is provided to evaluate the efficacy of treatment and to assist the user in improving his prescription of tobramycin or vancomycin. T(> MIC) (time the concentration remains above the MIC) and AUC(24) (area under the concentration-time curve) are calculated in plasma and tissues for azithromycin. In order to create a link between theoretical pharmacokinetics and clinical practice, we propose this model as a simulation of antibiotic monitoring. We put the emphasis on interactivity and simulation, leading to applied reasoning and decision making. It illustrates (i) the influence of pharmacokinetic parameters, location of infection and bactericidal kinetics on the use of three different classes of antibiotics, (ii) the role of route of administration, dosing and intervals between administrations on therapeutic response and (iii) the influence of erratic administrations on clinical efficacy.

Anti-Bacterial Agents↗

PubMed2002

Association between initial empirical therapy and decreased length of stay among veteran patients hospitalized with community acquired pneumonia.

This investigation assessed the impact of initial empirical antimicrobial therapy on the outcome of therapy for community acquired pneumonia (CAP) patients and on patients' length of stay (LOS) in the hospital. Hospital records for 165 patients with pneumonia admitted to the Edward Hines, Jr. VA Hospital between 1 October 1997, and 31 March 2000, were reviewed. Criteria for CAP were met for 92 of 165 patients. Comparisons were made between patients treated with azithromycin and with other parenteral antibiotics (the reference group). No statistical differences were observed between the treatment groups for the risk factors. The azithromycin group patients were slightly older with a mean age of 69 years versus 66 years (P=0.23). Patients treated with parenteral azithromycin had on average, a shorter length of hospitalization namely 4.6 days compared with 9.7 days for patients treated with the other antibiotics (log-rank test, P=0.0001). In order to make the two groups of patients more alike we considered patients' data set without intensive care unit (ICU) admissions. The conclusion was the same namely azithromycin monotherapy was associated with a decreased duration of hospital stay.

Aged↗

PubMed2003

Improved lung function and body mass index associated with long-term use of Macrolide antibiotics.

BACKGROUND: A number of studies have suggested that the non-antimicrobial actions of macrolide antibiotics may be valuable in treating patients with cystic fibrosis. The use of long-term macrolide antibiotics for the management of CF patients colonised by Pseudomonas aeruginosa and progressive pulmonary disease was introduced into our clinic in 1997. A retrospective study was undertaken to assess of the impact of this therapy. METHODS: Twenty patients with progressive pulmonary disease (>10% fall in FEV(1) over 12 months despite optimising conventional therapy) were commenced on Azithromycin, 250 mg daily during a 21-month period. At the time of assessment they had remained on therapy for a mean of 0.9 years. Changes in lung function, weight, body mass index (BMI) and frequency of pulmonary exacerbations were assessed. A group of 20 patients with stable lung function and matched as far as possible for age and sex was identified for comparison. RESULTS: Pulmonary function increased significantly in the Azithromycin group with FEV1% predicted increasing from a mean of 50.2-59.1% (P=0.001) while FVC% predicted increase from 64.5 to 76.1% (P=0.002). There was small but non-significant fall in lung function in the comparison group. Body mass index increased by a mean of 1.1 in the Azithromycin group but remained unchanged in the comparison group. The number of pulmonary exacerbations requiring intravenous antibiotics declined by 48.3% in macrolide treated subjects compared to the pre-treatment period (P<0.025); frequency of exacerbations in the control group was unchanged. CONCLUSION: Long-term Azithromycin treatment in patients with progressive deterioration in lung function appears to have led to an improvement in pulmonary function, increased body mass index and decreased the frequency of pulmonary exacerbations requiring intravenous antibiotics.

Adolescent↗

PubMed2000

The periodontal abscess (II). Short-term clinical and microbiological efficacy of 2 systemic antibiotic regimes.

BACKGROUND/AIMS: The aim of this short-term open parallel longitudinal clinical study was to compare the clinical and microbiological efficacy of 2 different antibiotic regimes in the treatment of acute periodontal abscesses. METHOD: After patient selection, a clinical examination was carried out recording the following variables: pain, edema, redness, swelling, bleeding on probing, suppuration, tooth mobility, lymphadenopathy, and probing pocket depth. Microbiological samples were taken from the lesion and the patient was randomly assigned to one of two antibiotic regimes: azithromycin or amoxicillin/clavulanate. Clinical variables were recorded, and microbiological samples were taken, at 3-5 days, 10-12 days and 30 days. Additional mechanical treatment (debridement and scaling) was performed in the third visit (10-12 days). Blood and urine samples were collected at baseline and after 10-12 days. Microbiological samples were processed by anaerobic culturing, and isolated periodontal pathogens were tested for antibiotic susceptibility by means of the spiral gradient endpoint methodology. RESULTS: 15 patients took azithromycin, and 14 amoxicillin/clavulanate. Subjective clinical variables demonstrated statistically significant improvements with both antibiotic regimes, which lasted for at least 1 month (p<0.01). Objective clinical variables also showed clear improvements, being statistically significant after 30 days with probing pocket depth in the azithromycin group (p<0.01). Microbiologically, short-term reductions were detected with both antibiotics, however fast recolonization occurred after the third visit. No significant differences were found between both treatment regimes. Antibiotic susceptibilities demonstrated no resistances for amoxicillin/clavulanate, while 2-3 strains of each studied pathogen were resistant to azithromycin. CONCLUSIONS: However, both antibiotic regimes were effective in the short-term treatment of periodontal abscesses in periodontitis patients.

Acute Disease↗

PubMed2001

QT prolongation associated with azithromycin/amiodarone combination.

Administration of oral azithromycin, in addition to previously well-tolerated long-term amiodarone therapy, was associated with a marked prolongation of QT interval and increased QT dispersion, both substrates for life-threatening ventricular tachyarrhythmia and torsades de pointes. This is a report of QT prolongation and increased QT dispersion associated with the use of azithromycin. The report assumes an added significance, in view of widespread empirical use of this antibiotic for the treatment of lower respiratory infections and belief of its safety in patients with cardiac diseases. Based on the authors' experience, they would like to emphasize that the combination of azithromycin with other drugs known to prolong QT or causing torsades de pointes be used with caution until the question of the proarrhythmic effect of azithromycin is resolved by further studies.

Aged↗

PubMed2001

Trachoma: a review.

Trachoma is a leading cause of preventable blindness worldwide. The disease is caused by an intracellular epithelial gram-negative bacterium, Chlamydia trachomatis. The presence of children, overcrowding, and the lack of water in the household are factors that predispose to the transmission of the disease. The disease may remain asymptomatic but some patients many complain of redness, irritation, and ocular discharge. The principal initial clinical manifestation is a follicular conjunctivitis that may lead to conjunctival scarring, entropion, trichiasis, corneal thinning, and ulceration. Some patients develop corneal scars that lead to loss of vision. Despite the remarkable progress in our understanding of Chlamydial infections, the basic mechanisms involved in tissue damage and scarring remain to be elucidated. There are several effective therapeutic modalities for trachoma. Azithromycin oral single dose was found to be safe and effective in children with active trachoma. Conjunctival biopsy specimens obtained from adult patients receiving a single oral dose of azithromycin showed sustained high levels of azithromycin (above MIC of chlamydia) for up to 2 weeks after intake. These prolonged high levels of azithromycin in the conjunctival tissue following a single oral dose makes the drug suitable for the treatment of endemic trachoma.

Administration, Oral↗

PubMed2002

Treatment of uncomplicated genital Chlamydia trachomatis infections in adults.

To prepare the 2001 sexually transmitted disease treatment guidelines of the Centers for Disease Control and Prevention, recently published articles and abstracts concerning advances in the treatment of uncomplicated Chlamydia trachomatis genital infections in adults were reviewed. Questions about treatments were posed and answered according to the results of efficacy studies and clinical trials. Recent studies have continued to demonstrate the similar efficacy of doxycycline and azithromycin. Because compliance with doxycyline remains a concern, administration of single-dose azithromycin therapy in the clinic presents a potential advantage for patients whose adherence is questionable. Because few systematically collected data have been published concerning the safety and efficacy of azithromycin use in pregnancy, the guidelines continue to recommend treatment with erythromycin or amoxicillin. Nevertheless, because of azithromycin's less frequent side effects and improved adherence, increasing numbers of obstetricians in the United States are using azithromyin to treat pregnant women with uncomplicated C. trachomatis infections.

Adult↗

PubMed2003

Factors associated with relative rates of antimicrobial resistance among Streptococcus pneumoniae in the United States: results from the TRUST Surveillance Program (1998-2002).

To identify factors associated with antimicrobial resistance, data were analyzed from 27,828 isolates of Streptococcus pneumoniae submitted to the Tracking Resistance in the United States Today (TRUST) surveillance program during 4 consecutive respiratory seasons. From the 1998-1999 season to the 2001-2002 season, the prevalence of azithromycin resistance increased by 4.8% to 27.5%, the prevalence of penicillin resistance increased by 3.7% to 18.4%, the prevalence of ceftriaxone resistance increased by 0.5% to 1.7%, and the prevalence of levofloxacin resistance increased by 0.3% to 0.9%. Isolates recovered from patients <18 years of age and lower respiratory tract specimens had elevated rates of penicillin, azithromycin, and trimethoprim-sulfamethoxazole resistance (P<.00001); penicillin resistance correlated with coresistance to trimethoprim-sulfamethoxazole (87.3%), azithromycin (76.3%), ceftriaxone (9.1%), and levofloxacin (1.3%) (P<.00001). Only 62 (0.2%) of 27,828 isolates were concurrently resistant to penicillin and levofloxacin. Minimum inhibitory concentrations (MICs) of penicillin correlated strongly with MICs of ceftriaxone (R2=0.90), trimethoprim-sulfamethoxazole (R2=0.53), and azithromycin (R2=0.41). Patient age, specimen source, and penicillin resistance were factors associated with antimicrobial resistance, particularly for nonfluoroquinolone antimicrobial agents.

Adolescent↗