Azithromycin :: therapeutic use
Latest Paper:
University of Kentucky, Lexington, 40536, USA.
Drug acquisition cost is an important component in the analysis of economic and clinical outcomes in the treatment of respiratory tract infections (RTIs). However, bacterial resistance has emerged as a crucial variable that must also be considered. Drug-resistant infections result in more expensive drug therapy, longer hospital stays, and increased mortality. The high prevalence of community-acquired pneumonia (CAP), as well as the continuing growth in resistant pathogens, make RTIs an appropriate model for studying methods of cost-containment without sacrificing clinical outcome. The University of Kentucky Medical Center has developed a uniform CAP treatment pathway to minimize costs and maximize outcomes. First-line therapy in this model is doxycycline monotherapy, high-dose amoxicillin plus azithromycin, or levofloxacin monotherapy. One major future concern in selecting antibacterial agents for CAP is the spread of macrolide- and fluoroquinolone-resistant Streptococcus pneumoniae.
Mesh-terms: Amoxicillin :: economics; Amoxicillin :: therapeutic use; Anti-Bacterial Agents :: economics; Anti-Bacterial Agents :: therapeutic use; Azithromycin :: economics; Azithromycin :: therapeutic use; Community-Acquired Infections :: drug therapy; Community-Acquired Infections :: economics; Community-Acquired Infections :: microbiology; Doxycycline :: economics; Doxycycline :: therapeutic use; Drug Resistance, Multiple, Bacterial :: drug effects; Humans; Kentucky; Ofloxacin :: therapeutic use; Pneumonia, Bacterial :: drug therapy; Pneumonia, Bacterial :: economics; Pneumonia, Bacterial :: microbiology; Respiratory Tract Infections :: drug therapy; Respiratory Tract Infections :: economics; Respiratory Tract Infections :: microbiology; Streptococcus pneumoniae :: drug effects; Treatment Outcome; United States;
Most cited papers:
University of Utah, LDS Hospital, Salt Lake City 84143, USA.
BACKGROUND: Chlamydia pneumoniae infection has been associated with atherosclerosis by serological studies and detection of bacterial antigen within plaque. We sought to evaluate a possible causal role in an animal model. METHODS AND RESULTS: Thirty New Zealand White rabbits were given three separate intranasal inoculations of either C pneumoniae (n = 20) or saline (n = 10) at 3-week intervals and fed chow enriched with a small amount ( .25%) of cholesterol. Immediately after the final inoculation, infected and control rabbits were randomized and begun on a 7-week course of azithromycin or no therapy. Three months after the final inoculation, rabbits were euthanatized and sections of thoracic aortas were blindly evaluated microscopically for maximal intimal thickness (MIT), percentage of luminal circumference involved (PLCI), and plaque area index (PAI) of atherosclerosis. Vascular chlamydial antigen was assessed by direct immunofluorescence. MIT differed among treatment groups (P=.009), showing an increase in infected rabbits ( .55 mm; SE = .15 mm) compared with uninfected controls ( .16 mm; SE = .06 mm) and with infected rabbits receiving antibiotics ( .20 mm; SE = .03 mm)(both P<.025), whereas MIT in infected/treated versus control rabbits did not differ. PLCI also tended to differ (P<.1) and PAI differed significantly (P<.01) among groups with a similar pattern. Chlamydial antigen was detected in 2 untreated, 3 treated, and control animals. CONCLUSIONS: Intranasal C pneumoniae infection accelerates intimal thickening in rabbits given a modestly cholesterol-enhanced diet. In addition, weekly treatment with azithromycin after infectious exposure prevents accelerated intimal thickening. These findings strengthen the etiologic link between C pneumoniae and atherosclerosis and should stimulate additional animal and human studies, including clinical antibiotic trials.
Mesh-terms: Animals; Anti-Bacterial Agents :: therapeutic use; Antigens, Bacterial :: analysis; Aorta :: microbiology; Aorta :: pathology; Arteriosclerosis :: etiology; Arteriosclerosis :: microbiology; Arteriosclerosis :: pathology; Arteriosclerosis :: prevention & control; Azithromycin :: therapeutic use; Chlamydia Infections :: complications; Chlamydia Infections :: drug therapy; Chlamydophila pneumoniae :: pathogenicity; Comparative Study; Female; Fluorescent Antibody Technique, Indirect; Human; Rabbits; Specific Pathogen-Free Organisms; Support, Non-U.S. Gov't;
D V Havlir,
M P Dubé,
F R Sattler,
D N Forthal,
C A Kemper,
M W Dunne,
D M Parenti,
J P Lavelle,
A C White Jr,
M D Witt,
S A Bozzette,
J A McCutchan
BACKGROUND: Azithromycin is active in treating Mycobacterium avium complex disease, but it has not been evaluated as primary prophylaxis in patients with human immunodeficiency virus (HIV) infection. Because the drug is concentrated in macrophages and has a long half-life in tissue, there is a rationale for once-weekly dosing. METHODS: We compared three prophylactic regimens in a multicenter, double-blind, randomized trial involving 693 HIV-infected patients with fewer than 100 CD4 cells per cubic millimeter. The patients were assigned to receive rifabutin (300 mg daily), azithromycin (1200 mg weekly), or both drugs. They were monitored monthly with blood cultures for M. avium complex. RESULTS: In an intention-to-treat analysis, the incidence of disseminated M. avium complex infection at one year was 15.3 percent with rifabutin, 7.6 percent with azithromycin, and 2.8 percent with both drugs. The risk of the infection in the azithromycin group was half that in the rifabutin group (hazard ratio, .53; P = .008). The risk was even lower when two-drug prophylaxis was compared with rifabutin alone (hazard ratio, .28; P< .001) or azithromycin alone (hazard ratio, .53; P = .03). Among the patients in whom azithromycin prophylaxis was not successful, 11 percent of M. avium complex isolates were resistant to azithromycin. Dose-limiting toxic effects were more common with the two-drug combination than with azithromycin alone (hazard ratio, 1.67; P= .03). Survival was similar in all three groups. CONCLUSIONS: For protection against disseminated M. avium complex infection, once-weekly azithromycin is more effective than daily rifabutin and infrequently selects for resistant isolates. Rifabutin plus azithromycin is even more effective but is not as well tolerated.
Mesh-terms: AIDS-Related Opportunistic Infections :: microbiology; AIDS-Related Opportunistic Infections :: prevention & control; Adult; Anti-Bacterial Agents :: administration & dosage; Anti-Bacterial Agents :: adverse effects; Anti-Bacterial Agents :: therapeutic use; Antibiotics, Antitubercular :: administration & dosage; Antibiotics, Antitubercular :: adverse effects; Antibiotics, Antitubercular :: therapeutic use; Azithromycin :: administration & dosage; Azithromycin :: adverse effects; Azithromycin :: therapeutic use; Comparative Study; Double-Blind Method; Drug Resistance, Microbial; Drug Therapy, Combination; Female; HIV Infections :: complications; Human; Male; Mycobacterium avium Complex :: drug effects; Mycobacterium avium Complex :: isolation & purification; Mycobacterium avium-intracellulare Infection :: microbiology; Mycobacterium avium-intracellulare Infection :: prevention & control; Rifabutin :: administration & dosage; Rifabutin :: adverse effects; Rifabutin :: therapeutic use; Support, Non-U.S. Gov't;
Breakthrough pneumococcal bacteremia in patients being treated with azithromycin and clarithromycin.
Streptococcus pneumoniae strains have exhibited decreasing susceptibility to penicillins and macrolides during the past several years. We reviewed the medical charts of all patients with pneumococcal bacteremia who were admitted to a university hospital over a period of 1 year, to identify failures of outpatient therapy. Of 41 patients admitted with pneumococcal bacteremia, 4 had previously taken either azithromycin or clarithromycin for 3-5 days. All 4 had pneumococcal strains that exhibited low-level resistance to macrolide antibiotics. Among pneumococci, low-level resistance to macrolides can lead to clinical failure, and resistance to macrolides should be considered during the selection of empiric therapy for patients with presumed pneumococcal infections.
Mesh-terms: Aged; Anti-Bacterial Agents :: adverse effects; Anti-Bacterial Agents :: therapeutic use; Azithromycin :: adverse effects; Azithromycin :: therapeutic use; Bacteremia :: drug therapy; Bacteremia :: etiology; Bacteremia :: microbiology; Child, Preschool; Clarithromycin :: adverse effects; Clarithromycin :: therapeutic use; Drug Resistance, Microbial; Female; Human; Male; Middle Aged; Pneumococcal Infections :: drug therapy; Pneumococcal Infections :: microbiology; Streptococcus pneumoniae :: drug effects; Streptococcus pneumoniae :: isolation & purification; Treatment Failure;
J Thomas Grayston,
Richard A Kronmal,
Lisa A Jackson,
Alfred F Parisi,
Joseph B Muhlestein,
Jerome D Cohen,
William J Rogers,
John R Crouse,
Sandra L Borrowdale,
Eleanor Schron,
Charles Knirsch
BACKGROUND: Epidemiologic, laboratory, animal, and clinical studies suggest that there is an association between Chlamydia pneumoniae infection and atherogenesis. We evaluated the efficacy of one year of azithromycin treatment for the secondary prevention of coronary events. METHODS: In this randomized, prospective trial, we assigned 4012 patients with documented stable coronary artery disease to receive either 600 mg of azithromycin or placebo weekly for one year. The participants were followed for a mean of 3.9 years at 28 clinical centers throughout the United States. RESULTS: The primary end point, a composite of death due to coronary heart disease, nonfatal myocardial infarction, coronary revascularization, or hospitalization for unstable angina, occurred in 446 of the participants who had been randomly assigned to receive azithromycin and 449 of those who had been randomly assigned to receive placebo. There was no significant risk reduction in the azithromycin group as compared with the placebo group with regard to the primary end point (risk reduction, 1 percent [95 percent confidence interval,-13 to 13 percent]). There were also no significant risk reductions with regard to any of the components of the primary end point, death from any cause, or stroke. The results did not differ when the participants were stratified according to sex, age, smoking status, presence or absence of diabetes mellitus, or C. pneumoniae serologic status at baseline. CONCLUSIONS: A one-year course of weekly azithromycin did not alter the risk of cardiac events among patients with stable coronary artery disease.
Mesh-terms: Aged; Anti-Bacterial Agents :: adverse effects; Anti-Bacterial Agents :: therapeutic use; Azithromycin :: adverse effects; Azithromycin :: therapeutic use; Chlamydophila Infections :: drug therapy; Chlamydophila pneumoniae; Coronary Disease :: drug therapy; Coronary Disease :: mortality; Coronary Disease :: prevention & control; Double-Blind Method; Female; Hearing Loss :: chemically induced; Humans; Male; Middle Aged; Myocardial Infarction :: prevention & control; Myocardial Revascularization; Prospective Studies; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. ;
Division of Allergy and Infectious Diseases, University of Washington, School of Medicine, Seattle 98195, USA.
Chalmydia trachomatis infections are the most common bacterial sexually transmitted disease in the United States. A substantial proportion of initial infections in both men and women are asymptomatic. Use of nucleic acid amplification-based diagnostic tests on first-void urine makes it possible to initiate community-based screening programs aimed at identifying asymptomatically infected men and women. Directly observed single-dose therapy with azithromycin is now available. Screening programs have been demonstrated to reduce the overall prevalence of chlamydial infection in the tested population and to reduce the incidence of subsequent pelvic inflammatory disease in previously screened women. The sequelae of chlamydial infections are likely due to immunopathologically mediated events in which both the chlamydial 60 kDa heat-shock protein and genetic predisposition of specific patients play a role. An improved understanding of immunologic events leading to upper genital tract scarring is needed to target specific interventions and facilitate development of a vaccine.
Mesh-terms: Anti-Bacterial Agents :: therapeutic use; Azithromycin :: therapeutic use; Chlamydia Infections :: diagnosis; Chlamydia Infections :: drug therapy; Chlamydia Infections :: etiology; Chlamydia trachomatis :: genetics; Chlamydia trachomatis :: immunology; Chlamydia trachomatis :: isolation & purification; DNA, Bacterial :: genetics; DNA, Bacterial :: isolation & purification; Female; Human; Male; Mass Screening; Support, U.S. Gov't, P.H.S. ;
Division of Infectious Diseases, Emory University School of Medicine, Atlanta, Georgia 30333, USA.
In vitro susceptibility testing and genotyping were done on urogenital isolates of Chlamydia trachomatis from 3 patients, 2 of whom showed evidence of clinical treatment failure with azithromycin and one of whom was the wife of a patient. All 3 isolates demonstrated multidrug resistance to doxycycline, azithromycin, and ofloxacin at concentrations >4. microg/mL. Recurrent disease due to relapsing infection with the same resistant isolate was documented on the basis of identical genotypes of both organisms. This first report of clinically significant multidrug-resistant C. trachomatis causing relapsing or persistent infection may portend an emerging problem to clinicians and public health officials.
Mesh-terms: Adolescent; Anti-Bacterial Agents :: therapeutic use; Anti-Infective Agents :: therapeutic use; Azithromycin :: therapeutic use; Chlamydia Infections :: drug therapy; Chlamydia trachomatis :: classification; Chlamydia trachomatis :: drug effects; Chlamydia trachomatis :: genetics; Disease Transmission, Horizontal; Drug Resistance, Multiple; Female; Human; Male; Microbial Sensitivity Tests; Ofloxacin :: therapeutic use; Pregnancy; Pregnancy Complications, Infectious; Urethritis :: drug therapy; Urethritis :: microbiology;
A L Kozyrskyj,
G E Hildes-Ripstein,
S E Longstaffe,
J L Wincott,
D S Sitar,
T P Klassen,
M E Moffatt
OBJECTIVE: To conduct a meta-analysis of randomized controlled trials of antibiotic treatment of acute otitis media in children to determine whether outcomes were comparable in children treated with antibiotics for less than 7 days or at least 7 days or more. DATA SOURCES: MEDLINE (1966-1997), EMBASE (1974-1997), Current Contents, and Science Citation Index searches were conducted to identify randomized controlled trials of the treatment of acute otitis media in children with antibiotics of different durations. STUDY SELECTION: Studies were included if they met the following criteria: subjects aged 4 weeks to 18 years, clinical diagnosis of acute otitis media, no antimicrobial therapy at time of diagnosis, and randomization to less than 7 days of antibiotic treatment vs 7 days or more of antibiotic treatment. DATA EXTRACTION: Trial methodological quality was assessed independently by 7 reviewers; outcomes were extracted as the number of treatment failures, relapses, or reinfections. DATA SYNTHESIS: Included trials were grouped by antibiotic used in the short course:(1) 15 short-acting oral antibiotic trials (penicillin V potassium, amoxicillin [-clavulanate], cefaclor, cefixime, cefuroxime, cefpodoxime proxetil, cefprozil),(2) 4 intramuscularceftriaxone sodium trials, and (3) 11 oral azithromycin trials. The summary odds ratio for treatment outcomes at 8 to 19 days in children treated with short-acting antibiotics for 5 days vs 8 to 10 days was 1.52 (95% confidence interval [CI], 1.17-1.98) but by 20 to 30 days outcomes between treatment groups were comparable (odds ratio, 1.22; 95% CI, .98 to 1.54). The risk difference (2.3%; 95% CI,- .2% to 4.9%) at 20 to 30 days suggests that 44 children would need to be treated with the long course of short-acting antibiotics to avoid 1 treatment failure. This similarity in later outcomes was observed for up to 3 months following therapy (odds ratio, 1.16; 95% CI, .90-1.50). Comparable outcomes were shown between treatment with ceftriaxone or azithromycin, and at least 7 days of other antibiotics. CONCLUSION: This meta-analysis suggests that 5 days of short-acting antibiotic use is effective treatment for uncomplicated acute otitis media in children.
Mesh-terms: Acute Disease; Anti-Bacterial Agents :: administration & dosage; Anti-Bacterial Agents :: therapeutic use; Azithromycin :: administration & dosage; Azithromycin :: therapeutic use; Ceftriaxone :: administration & dosage; Ceftriaxone :: therapeutic use; Cephalosporins :: administration & dosage; Cephalosporins :: therapeutic use; Child; Drug Administration Schedule; Human; Otitis Media :: drug therapy; Randomized Controlled Trials; Support, Non-U.S. Gov't; Treatment Outcome;
Laboratory Centre for Disease Control Health, Winnipeg, Manitoba, Canada. rosanna_peeling@isdtcp3.hwc.ca
The recognition of genital chlamydial infection as an important public health problem was made first by the recognition of its role in acute clinical syndromes, as well as in serious reproductive and ocular complications, and secondly by our awareness of its prevalence when diagnostic tests became widely accessible. The recent availability of effective single dose oral antimicrobial therapy and sensitive molecular amplification tests that allow the use of noninvasive specimens for diagnosis and screening is expected to have a major impact in reducing the prevalence of disease in the next decade. Clinical manifestations associated with Chlamydia pneumoniae infection continue to emerge beyond respiratory illness. In particular, its association with atherosclerosis deserves further investigation. Chlamydia pecorum, a pathogen of ruminants, was recently recognized as a new species. The continued application of molecular techniques will likely elucidate an expanding role for chlamydiae in human and animal diseases, delineate the phylogenetic relationships among chlamydial species and within the eubacteria domain, and provide tools for detection and control of chlamydial infections.
Mesh-terms: Anti-Bacterial Agents :: therapeutic use; Arteriosclerosis :: microbiology; Asthma :: microbiology; Azithromycin :: therapeutic use; Bacterial Outer Membrane Proteins :: genetics; Bacterial Outer Membrane Proteins :: immunology; Chlamydia Infections :: diagnosis; Chlamydia Infections :: drug therapy; Chlamydia Infections :: epidemiology; Chlamydia Infections :: microbiology; Chlamydia trachomatis :: genetics; Chlamydia trachomatis :: immunology; Chlamydia trachomatis :: pathogenicity; Chlamydophila pneumoniae :: pathogenicity; Chlamydophila psittaci :: pathogenicity; Clarithromycin :: therapeutic use; Host-Parasite Relations :: genetics; Human; Ornithosis :: diagnosis; Ornithosis :: drug therapy; Ornithosis :: epidemiology; Ornithosis :: microbiology; Polymorphism (Genetics) ; Tetracycline :: therapeutic use;
Infectious Disease Division, Johns Hopkins University, Baltimore City Health Department, Maryland, USA. cgaydos@welchlink.welch.jhu.edu
Polymerase chain reaction (PCR) and ligase chain reaction (LCR) were compared for the diagnosis of Chlamydia trachomatis infections by testing urine specimens from 408 high school female students. After therapy, sequential urine specimens were tested to determine persistence of chlamydial DNA in urine. Baseline PCR of cervical specimens was positive in 53 (13. %) students, and PCR and LCR of urine specimens were positive in 63 (15.4%) and 60 (14.7%), respectively. After discrepant analysis, 64 (15.7%) patients could be confirmed as truly infected. Follow-up urine specimens from 33 infected patients demonstrated that at 1-3 days after therapy, PCR and LCR were positive for 40% and 73.3%, respectively. Only at 15 days after therapy did all specimens test negative. Urine tests for Chlamydia organisms should not be used as a test of cure within 3 weeks after treatment. Use of urine assays for screening sexually active adolescents has the potential to significantly improve control of chlamydial infections.
Mesh-terms: Adolescent; Adult; Anti-Bacterial Agents :: therapeutic use; Azithromycin :: therapeutic use; Cervix Uteri :: microbiology; Chlamydia Infections :: diagnosis; Chlamydia Infections :: drug therapy; Chlamydia Infections :: urine; Chlamydia trachomatis :: genetics; Chlamydia trachomatis :: isolation & purification; DNA, Bacterial :: isolation & purification; Doxycycline :: therapeutic use; Female; Follow-Up Studies; Human; Polymerase Chain Reaction :: methods; Schools; Sensitivity and Specificity; Support, U.S. Gov't, P.H.S. ;
R H Gray,
F Wabwire-Mangen,
G Kigozi,
N K Sewankambo,
D Serwadda,
L H Moulton,
T C Quinn,
K L O'Brien,
M Meehan,
C Abramowsky,
M Robb,
M J Wawer
Department of Population and Family Health Sciences, The Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Md 21205, USA. rgray@jhsph.edu
OBJECTIVE: The purpose of this study was to assess presumptive sexually transmitted disease treatment on pregnancy outcome and HIV transmission. STUDY DESIGN: In a randomized trial in Rakai District, Uganda, 2070 pregnant women received presumptive sexually transmitted disease treatment 1 time during pregnancy at varying gestations, and 1963 control mothers received iron/folate and referral for syphilis. Maternal-infant sexually transmitted disease/HIV and infant outcomes were assessed. Intent-to-treat analyses estimated adjusted rate ratios and 95% confidence intervals. RESULTS: Sexually transmitted diseases were reduced: Trichomonas vaginalis (rate ratio, .28; 95% CI, .18%- .49%), bacterial vaginosis (rate ratio, .78; 95% CI, .69- .87), Neisseria gonorrhoeae /Chlamydia trachomatis (rate ratio, .43; 95% CI, .27- .68), and infant ophthalmia (rate ratio, .37; 95% CI, .20- .70). There were reduced rates of neonatal death (rate ratio, .83; 95% CI, .71- .97), low birth weight (rate ratio, .68; 95% CI, .53- .86), and preterm delivery (rate ratio, .77; 95% CI, .56-1.05); but there were no effects on maternal HIV acquisition or perinatal HIV transmission. CONCLUSION: Reductions of maternal sexually transmitted disease improved pregnancy outcome but not maternal HIV acquisition or perinatal HIV transmission.
Mesh-terms: Azithromycin :: therapeutic use; Birth Weight; Cefixime :: therapeutic use; Comparative Study; Drug Therapy, Combination; Endophthalmitis :: prevention & control; Female; Folic Acid :: therapeutic use; HIV Infections :: therapy; Human; Infant; Infant Mortality; Infant, Newborn; Infant, Newborn, Diseases :: prevention & control; Infant, Premature; Iron :: therapeutic use; Labor, Premature :: prevention & control; Metronidazole :: therapeutic use; Pregnancy; Pregnancy Complications, Infectious :: therapy; Sexually Transmitted Diseases :: prevention & control; Sexually Transmitted Diseases :: therapy; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S. ; Uganda;
