rifampin and Chlamydia-Infections

Topics: Adult; Anti-Bacterial Agents; Anti-Infective Agents; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Reactive; Azithromycin; Chlamydia Infections; Chlamydia trachomatis; Diagnosis, Differential; Female; Haplotypes; HLA-B27 Antigen; Humans; Magnetic Resonance Imaging; Male; Polymerase Chain Reaction; Prognosis; Rifampin; Sulfasalazine; Time Factors; Urine

Rifalazil is a benzoxazinorifamycin which inhibits bacterial DNA-dependent RNA polymerase. The benzoxazine ring endows benzoxazinorifamycins with unique physical and chemical characteristics which favor the use of rifalazil and derivatives in treating diseases caused by the obligate intracellular pathogens of the genus chlamydia. Minimal inhibitory concentrations of benzoxazinorifamycins against chlamydia are in the pg/mL range. These compounds have potential as monotherapeutic agents to treat chlamydia-associated disease because they retain activity against chlamydia strains resistant to currently approved rifamycins such as rifampin. A pivotal clinical trial with rifalazil has been initiated for the treatment of peripheral arterial disease. The rationale for this innovative use of rifalazil, including the association of C. pneumoniae in atherosclerotic plaque formation, as well as rifalazil's potency and efficacy against chlamydia in both preclinical and clinical studies, is discussed. Other benzoxazino derivatives may have utility as stand-alone topical antibacterials or combination antibacterials to treat serious Gram-positive infections. None of the benzoxazinorifamycins examined to date induce the cytochrome P450 3A4 enzyme. This is in contrast to currently approved rifamycins which are strong inducers of P450 enzymes, resulting in drug-drug interactions that limit the clinical utility of this drug class.

Topics: Animals; Anti-Bacterial Agents; Atherosclerosis; Chlamydia Infections; Chlamydophila pneumoniae; Humans; Peripheral Vascular Diseases; Rifampin; Rifamycins

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Antibodies, Bacterial; Arthritis, Reactive; Azithromycin; Chlamydia Infections; Chlamydia trachomatis; Ciprofloxacin; Clinical Trials as Topic; Diagnosis, Differential; DNA, Bacterial; Drug Therapy, Combination; Enteritis; Female; Humans; Male; Models, Theoretical; Polymerase Chain Reaction; Rifampin; Salmonella; Salmonella Infections; Sensitivity and Specificity; Tetracyclines; Time Factors; Urethritis; Uterine Cervicitis; Yersinia; Yersinia Infections

Chlamydia trachomatis and Chlamydophila (Chlamydia) pneumoniae are known triggers of reactive arthritis (ReA) and exist in a persistent metabolically active infection state in the synovium, suggesting that they may be susceptible to antimicrobial agents. The goal of this study was to investigate whether a 6-month course of combination antibiotics is an effective treatment for patients with chronic Chlamydia-induced ReA.. This study was a 9-month, prospective, double-blind, triple-placebo trial assessing a 6-month course of combination antibiotics as a treatment for Chlamydia-induced ReA. Eligible patients had to be positive for C trachomatis or C pneumoniae by polymerase chain reaction (PCR). Groups received 1) doxycycline and rifampin plus placebo instead of azithromycin; 2) azithromycin and rifampin plus placebo instead of doxycycline; or 3) placebos instead of azithromycin, doxycycline, and rifampin. The primary end point was the number of patients who improved by 20% or more in at least 4 of 6 variables without worsening in any 1 variable in both combination antibiotic groups combined and in the placebo group at month 6 compared with baseline.. The primary end point was achieved in 17 of 27 patients (63%) receiving combination antibiotics and in 3 of 15 patients (20%) receiving placebo. Secondary efficacy end points showed similar results. Six of 27 patients (22%) randomized to combination antibiotics believed that their disease went into complete remission during the trial, whereas no patient in the placebo arm achieved remission. Significantly more patients in the active treatment group became negative for C trachomatis or C pneumoniae by PCR at month 6. Adverse events were mild, with no significant differences between the groups.. These data suggest that a 6-month course of combination antibiotics is an effective treatment for chronic Chlamydia-induced ReA.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotics, Antitubercular; Arthritis, Reactive; Azithromycin; Chlamydia Infections; Chlamydia trachomatis; Chlamydophila pneumoniae; Chronic Disease; DNA, Bacterial; Double-Blind Method; Doxycycline; Drug Therapy, Combination; Female; Humans; Joints; Male; Middle Aged; Placebos; Prohibitins; Prospective Studies; Rifampin; Treatment Outcome

To assess whether doxycycline and rifampin have a therapeutic role in patients with Alzheimer's disease (AD).. Randomized, triple-blind, controlled trial.. Three tertiary care and two community geriatric clinics in Canada.. One hundred one patients with probable AD and mild to moderate dementia.. Oral daily doses of doxycycline 200 mg and rifampin 300 mg for 3 months.. The primary outcome was a change in Standardized Alzheimer's Disease Assessment Scale cognitive subscale (SADAScog) at 6 months. Secondary outcomes were changes in the SADAScog at 12 months and tests of dysfunctional behavior, depression, and functional status.. There was significantly less decline in the SADAScog score at 6 months in the antibiotic group than in the placebo group, (-2.75 points, 95% confidence interval (CI)=-5.28 to -0.22, P=.034). At 12 months, the difference between groups in the SADAScog was -4.31 points (95% CI=-9.17-0.56, P=.079). The antibiotic group showed significantly less dysfunctional behavior at 3 months. There was no significant difference in adverse events between groups (P=.34). There were no differences in Chlamydia pneumoniae detection using polymerase chain reaction or antibodies (immunoglobulin (Ig)G or IgA) between groups.. Therapy with doxycycline and rifampin may have a therapeutic role in patients with mild to moderate AD. The mechanism is unlikely to be due to their effect on C. pneumoniae. More research is needed to investigate these agents.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Anti-Bacterial Agents; Chlamydia Infections; Chlamydophila pneumoniae; Dementia; Doxycycline; Female; Humans; Male; Middle Aged; Rifampin

Chlamydia is a known trigger of reactive arthritis (ReA). It may also be common cause of undifferentiated spondyloarthropathy (uSpA). Persistent, metabolically active, Chlamydiae have been observed in the synovial tissue of these patients years after their initial exposure. Trials with lymecycline and rifampin have shown benefit in early/acute Chlamydia-induced arthritis. In vitro data suggest that persistent Chlamydia become resistant to chronic monotherapy of tetracyclines or rifampin, whereas no such resistance is noted when rifampin is added to antimicrobials that are active against Chlamydia. Rifampin and doxycycline also show synergistic effect against Chlamydia. In addition, rifampin inhibits chlamydial production of heat shock proteins (HSP). HSP60 plays a key role in the chronic persistent state of Chlamydia. We conducted a prospective, randomized 9-month trial to evaluate the efficacy of doxycycline versus a combination of doxycycline and rifampin in the treatment of uSpA.. The study enrolled 30 patients with chronic inflammatory arthritis (average disease duration 10 yrs) who fulfilled the European Spondylarthropathy Study Group criteria, with no evidence of inflammatory bowel disease, psoriasis, ankylosing spondylitis, or preceding dysentery. Patients received doxycycline 100 mg po twice daily or a combination of doxycycline 100 mg po twice daily and rifampin 600 mg po daily. They received a 4-question self-questionnaire and a blinded joint examination at each visit. The questions include a visual analog scale (VAS) for their current amount of back pain, duration of morning stiffness, back pain at night, and peripheral joint pain. The blinded joint examination consisted of a swollen joint count (SJC) and a tender joint count (TJC). These 6 variables were assessed at baseline and at 1, 3, 6, and 9 months. Responders were defined as those who improved > or = 20% in at least 4 of the 6 variables at 9 months of therapy.. Comparing the doxycycline + rifampin arm (D/R) versus the doxycycline arm (D) at 9 months of therapy, all 6 variables improved more in D/R versus D, 4 of which were statistically significant. The mean VAS (scale of 100) decreased 24.4 points in D/R in contrast to 3 points in D (p < 0.03). Duration of morning stiffness decreased by 1.2 h in D/R, with a slight increase of 0.1 h in D (p < 0.003). The back pain at night and peripheral joint pain both improved in D/R group versus D (not statistically significant). Finally, the SJC and TJC also improved in D/R (-2.1 and -2.5) versus D (-0.4 and -0.6; p = 0.02, p = 0.03, respectively). Eleven of 15 patients in the D/R arm were responders, whereas only 2 of 15 D group patients were considered responders (p < 0.003).. The combination of doxycycline and rifampin for 9 months seemed to be effective in treatment of chronic uSpA. This is the first study to demonstrate therapeutic benefit with antimicrobials to a chronic inflammatory arthritis possibly secondary to persistent Chlamydia.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotics, Antitubercular; Arthritis, Reactive; Chlamydia Infections; Doxycycline; Drug Synergism; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pain Measurement; Prohibitins; Prospective Studies; Retrospective Studies; Rifampin; Spondylarthropathies; Surveys and Questionnaires

The data on the incidence of Chlamydia and Mycoplasma infections in children with inflammatory diseases of the respiration organs are presented. The peculiarities of the clinical manifestations and the attempts to carry out the clinical differential diagnostication are described. The chemotherapeutic efficacies of erythromycin, rifampicin and tetracycline in the treatment of pneumonia due to Chlamydia and Mycoplasma in children were studied. There was observed similarity in the clinical signs of the infections. The differential diagnostication without the data on the disease etiology was shown impossible. Marked chemotherapeutic efficacies of erythromycin and rifampicin in the treatment of chlamydiosis and mycoplasmosis in infants were stated. The tetracyclines were found to be efficient in the treatment of older children.

Topics: Age Distribution; Child, Preschool; Chlamydia Infections; Chlamydia trachomatis; Diagnosis, Differential; Erythromycin; Humans; Incidence; Infant; Infant, Newborn; Pneumonia, Mycoplasma; Respiratory Tract Diseases; Rifampin; Tetracyclines

A double-blind stratified trial was carried out on 85 patients to assess the efficacy of topical therapy with 1% chlortetracycline eye ointment in comparison with 1% rifampicin eye ointment in the treatment of chlamydial ocular infection of sexually transmitted origin (paratrachoma). Patients included were selected on the basis of positive culture for Chlamydia trachomatis. A 6-week course of treatment with chlortetracycline or rifampicin 3 times daily gave a clinical cure rate of 80% and 75% and a microbiological cure rate of 93% and 86% respectively. In patients who were not cured the intensity of inflammatory responses was considerably reduced.

Topics: Administration, Topical; Adolescent; Adult; Chlamydia Infections; Chlamydia trachomatis; Chlortetracycline; Clinical Trials as Topic; Conjunctivitis, Inclusion; Double-Blind Method; Female; Humans; Keratoconjunctivitis; Male; Middle Aged; Random Allocation; Rifampin; Trachoma

Chlamydia trachomatis and Chlamydia pneumoniae are intracellular bacterial pathogens that have been shown to cause, or are strongly associated with, diverse chronic diseases. Persistent infections by both organisms are refractory to antibiotic therapy. The lack of therapeutic efficacy results from the attenuated metabolic rate of persistently infecting chlamydiae in combination with the modest intracellular drug concentrations achievable by normal delivery of antibiotics to the inclusions within which chlamydiae reside in the host cell cytoplasm. In this research, we evaluated whether nanoparticles formulated using the biodegradable poly(d-L-lactide-co-glycolide) (PLGA) polymer can enhance the delivery of antibiotics to the chlamydial inclusion complexes. We initially studied the trafficking of PLGA nanoparticles in Chlamydia-infected cells. We then evaluated nanoparticles for the delivery of antibiotics to the inclusions. Intracellular trafficking studies show that PLGA nanoparticles efficiently concentrate in inclusions in both acutely and persistently infected cells. Further, encapsulation of rifampin and azithromycin antibiotics in PLGA nanoparticles enhanced the effectiveness of the antibiotics in reducing microbial burden. Combination of rifampin and azithromycin was more effective than the individual drugs. Overall, our studies show that PLGA nanoparticles can be effective carriers for targeted delivery of antibiotics to intracellular chlamydial infections.

Topics: Anti-Bacterial Agents; Azithromycin; Cell Line; Chemistry, Pharmaceutical; Chlamydia Infections; Chlamydia trachomatis; Coumarins; Dose-Response Relationship, Drug; Drug Delivery Systems; Drug Synergism; Humans; Intracellular Space; Lactic Acid; Microbial Sensitivity Tests; Microbial Viability; Nanoparticles; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer; Rifampin; Time Factors

An in vitro cell culture model was used to investigate the long-term effects of azithromycin, rifampin, and the combination of azithromycin and rifampin on Chlamydia trachomatis infection. Although standard in vitro susceptibility testing indicated efficient inhibition by azithromycin, prolonged treatment did not reveal a clear elimination of chlamydia from host cells. Chlamydia were temporarily arrested in a persistent state, characterized by culture-negative, but viable, metabolically active chlamydia, as demonstrated by the presence of short-lived rRNA transcripts. Additionally, azithromycin induced generation of aberrant inclusions and an altered steady-state level of chlamydial antigens, with the predominance of Hsp60 protein compared to the level of the major outer membrane protein. Treatment with azithromycin finally resulted in suppression of rRNA synthesis. Chlamydial lipopolysaccharide and processed, functional rRNA were detectable throughout the entire incubation period. These in vitro data show a good correlation to those from some recent clinical investigations that have reported on the persistence of chlamydia, despite appropriate antibiotic treatment with azithromycin. Rifampin was highly active by in vitro susceptibility testing, but prolonged exposure to rifampin alone for up to 20 days resulted in the emergence of resistance. No development of resistance to rifampin was observed when chlamydia-infected cells were incubated with a combination of azithromycin and rifampin. This combination was shown to be more efficient than azithromycin alone, in that suppression of rRNA synthesis occurred earlier. Thus, such a combination may prove more useful than azithromycin alone.

Topics: Anti-Bacterial Agents; Antibiotics, Antitubercular; Antigens, Bacterial; Azithromycin; Cell Line; Chlamydia Infections; Chlamydia trachomatis; Electrophoresis, Polyacrylamide Gel; Fluorescent Antibody Technique, Direct; Humans; Immunoblotting; Microbial Sensitivity Tests; Reverse Transcriptase Polymerase Chain Reaction; Rifampin; RNA, Ribosomal; Tumor Cells, Cultured

The effects of treatment with azithromycin plus rifampin (A+R), amoxicillin (A), or placebo (P) on the chronic course of experimental Chlamydia pneumoniae pneumonitis in mice were assessed by culture, PCR, and immunocytochemistry as well as by degree of inflammation in lung tissue. Eradication of the pathogen was significantly more frequent and inflammation in tissue was significantly reduced after treatment with A+R compared to after treatment with A or P. Combination therapy with azithromycin plus rifampin showed favorable effects in the chronic course of C. pneumoniae pneumonitis.

Topics: Amoxicillin; Animals; Anti-Bacterial Agents; Azithromycin; Chlamydia Infections; Chlamydophila pneumoniae; Drug Therapy, Combination; Mice; Pneumonia; Rifampin

Azithromycin, doxycycline, and rifampin, alone or in combination, were tested in vitro against Chlamydia pneumoniae AR-39. The combination of azithromycin plus rifampin showed the strongest activity and produced higher rates of eradication of C. pneumoniae from lung tissues than azithromycin alone in experimental mouse pneumonitis.

Topics: Animals; Azithromycin; Chlamydia Infections; Chlamydophila pneumoniae; DNA, Bacterial; Drug Therapy, Combination; Lung; Male; Mice; Pneumonia, Bacterial; Rifampin

In four patients with an adult chlamydial ophthalmia small, marginal corneal abscesses were detected. These corneal abscesses were associated with unilateral papillary and follicular conjunctivitis and punctate keratitis. In these patients no bacteria was isolated from the abscesses, but Chlamydia trachomatis was isolated from materials collected from the abscesses and from the conjunctival swabbings. In addition all patients had microbiologically proved concomitant chlamydial genital infections. The clinical signs resolved after topical treatment with rifampicin or tetracycline eye ointment for six weeks or systemic treatment with tetracycline for two weeks. Because of concomitant chlamydial genital infection it is advisable to treat patients with adult chlamydial ophthalmia with systemic tetracycline and to refer these patients and their consorts for investigation and treatment of their genital infection.

Topics: Abscess; Adult; Chlamydia Infections; Chlamydia trachomatis; Conjunctivitis, Inclusion; Corneal Diseases; Female; Humans; Keratitis; Male; Middle Aged; Rifampin; Tetracycline

Topics: Adult; Chlamydia Infections; Dentistry; Doxycycline; Female; Humans; Male; Occupational Diseases; Rifampin; Tetracycline

Topics: Chlamydia Infections; Dentists; Doxycycline; Humans; Occupational Diseases; Rifampin; Tetracyclines

Topics: Chlamydia Infections; Female; Humans; Male; Rifampin

Topics: Chlamydia Infections; Drug Resistance, Microbial; Drug Therapy, Combination; Haemophilus Infections; Humans; Meningitis, Meningococcal; Rifampin; Staphylococcal Infections; Trimethoprim

One hundred women with uncomplicated gonorrhoea (in five cases due to penicillinase producing strains of Neisseria gonorrhoeae (PPNG)) were treated with a single oral dose of rifampicin 900 mg and erythromycin stearate 1 g. N gonorrhoeae was reisolated from the oropharynx of one patient, who was infected with a PPNG strain, but was eradicated from the genital tract in 100% of cases. The combination eradicated Chlamydia trachomatis from only 10 (28%) of the 36 patients infected. Side effects were predominantly mild and consisted of transient nausea. The treatment merits evaluation in areas with a high incidence of PPNG strains.

Topics: Adolescent; Adult; Chlamydia Infections; Chlamydia trachomatis; Drug Therapy, Combination; Erythromycin; Female; Gonorrhea; Humans; Middle Aged; Rifampin

Topics: Antibodies, Bacterial; Bacteriological Techniques; Centrifugation; Chlamydia; Chlamydia Infections; Chloramphenicol; Clinical Laboratory Techniques; Complement Fixation Tests; Conjunctiva; Conjunctivitis, Inclusion; Culture Media; Fluorescent Antibody Technique; Humans; Independent State of Samoa; Indonesia; Methods; Rifampin; Trachoma; Tunisia