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Biomedical subjects

M R Hammerschlag

Publications and source records attributed to M R Hammerschlag.

At least 37 records · Page 2Linked to original sources

Is Chlamydia pneumoniae present in brain lesions of patients with multiple sclerosis?

We investigated the presence of Chlamydia pneumoniae in 81 normal and pathological specimens obtained from postmortem brain tissues of patients with multiple sclerosis and with other neurological or nonneurological diseases. The assays used included PCR amplification of all DNA samples in the initial study. Culture and a second PCR amplification of the organism in a subset of 19 brain specimens were also performed in two separate laboratories. All results were negative. Thus, this study on a large number of brain tissues suggests that C. pneumoniae is not involved in inflammatory demyelination.

Brain↗

Chlamydia pneumoniae and the lung.

Chlamydia pneumoniae is a frequently occurring respiratory pathogen affecting all age groups. It may cause 5-20% of community-acquired pneumonias in adults and children. The organism has also been implicated as an infectious trigger for asthma. Furthermore, new studies suggest that it may play a role in the pathogenesis of several chronic diseases including atherosclerosis. However, despite the growing significance of C. pneumoniae as a pathogen, progress is hampered by the lack of standardized diagnostic methods including serology and polymerase chain reaction. This makes it practically impossible for the practitioner to make a specific microbiological diagnosis. The lack of standardized methods has also had an adverse effect on treatment trials. The dependence on serology for diagnosis in treatment studies has generated some questionable results. Unless cultures are performed, microbiological efficacy cannot be assessed and it may never be possible to survey for or document the emergence of resistance.

Anti-Bacterial Agents↗

Activity of grepafloxacin and other fluoroquinones and newer macrolides against recent clinical isolates of Chlamydia pneumoniae.

Chlamydia pneumoniae is a frequent cause of community-acquired respiratory tract infection including pneumonia and bronchitis. Quinolones have attracted interest as potential therapy for community-acquired respiratory tract infections because they are active against a wide range of pathogens including C. pneumoniae and Mycoplasma pneumoniae. The in vitro susceptibilities of C. pneumoniae were determined for grepafloxacin, levofloxacin, moxifloxacin, trovafloxacin, clarithromycin and azithromycin. Isolates of C. pneumoniae tested included two reference strains, TW-183 and CM-1, and 12 recent clinical isolates from adults with community-acquired pneumonia. Susceptibility testing was performed in HEp-2 cells grown in 96-well microtiter plates. The MIC was the lowest antibiotic concentration at which no inclusions were seen. The MBC was the lowest concentration which resulted in no inclusions after passage in antibiotic-free medium. Grepafloxacin was the most active quinolone tested with an MIC50 of 0.125 mg/l, MIC90 and MBC90 of 0.5 mg/l. Grepafloxacin may have a role in the treatment of C. pneumoniae infections, but prospective clinical studies utilizing culture are lacking.

Adult↗

In-vitro activity of gatifloxacin against Chlamydia trachomatis and Chlamydia pneumoniae.

We compared the activity of gatifloxacin, a new quinolone, ofloxacin and erythromycin against five isolates of Chlamydia trachomatis and 20 isolates of Chlamydia pneumoniae, including TW183 and clinical isolates from the USA and Japan. Testing was done in cycloheximide-treated HEp-2 cells. Gatifloxacin was slightly less active against C. trachomatis and slightly more active against C. pneumoniae than ofloxacin, with MICs at which 90% of the isolates had no inclusions and minimal chlamydicidal concentrations at which 90% of the isolates had no inclusions after passage of 0.25 mg/L. Gatifloxacin was less active than erythromycin for both species.

Anti-Infective Agents↗

In vitro activities of gemifloxacin (SB 265805, LB20304) against recent clinical isolates of Chlamydia pneumoniae.

We compared the in vitro activity of gemifloxacin, a new quinolone antibiotic, to the activities of levofloxacin, moxifloxacin, trovafloxacin, erythromycin, and doxycycline against 20 isolates of Chlamydia pneumoniae. Gemifloxacin was the most active quinolone tested, with a MIC at which 90% of the isolates are inhibited and a minimal bactericidal concentration at which 90% of strains tested are killed of 0.25 microg/ml, but this activity was less than those of doxycycline and erythromycin.

Anti-Infective Agents↗

In vitro activities of azithromycin and ofloxacin against Chlamydia pneumoniae in a continuous-infection model.

Chlamydia pneumoniae is a well-established cause of community-acquired pneumonia and bronchitis in adults and children. Chronic infections with C. pneumoniae have been implicated in the development of atherosclerosis and other diseases in humans. Methods currently used for the culture and propagation of C. pneumoniae are not analogous to the infection as it occurs in vivo. We have established a model of continuous C. pneumoniae infection in vitro. HEp-2 cells inoculated with CM-1 and TW-183 strains have been persistently infected for periods of over 1.5 and 2 years, respectively. The cultures were maintained without centrifugation or the addition of cycloheximide, fresh host cells, or chlamydia. We observed cycles of host cell lysis, detachment, and regrowth with both strains of C. pneumoniae. Continuous C. pneumoniae infections may more closely resemble the actual events as they occur in vivo and, therefore, may be a better model for the in vitro study of C. pneumoniae infection. When we used continuously infected cells to determine the effects of azithromycin and ofloxacin on C. pneumoniae propagation in vitro, we found that both drugs reduced but did not completely eliminate the organism. This may be an important observation, as the failure of antibiotic therapy against C. pneumoniae infection in humans has been described.

Anti-Bacterial Agents↗

Inappropriate use of nonculture tests for the detection of Chlamydia trachomatis in suspected victims of child sexual abuse: A continuing problem.

The introduction of nonculture tests for detection of Chlamydia trachomatis has revolutionized the management of chlamydial infections in sexually active adolescents and adults. However, these tests are insufficiently specific for use in genital and rectal sites in children; false-positive tests can be frequent. We report here 4 cases involving inappropriate use of nonculture tests in children in New York City during 1998. Two cases involved the use of enzyme immunoassays with vaginal specimens. In both cases the initial results were positive, however, cultures for C trachomatis performed later were negative. In the third case, the DNA probe test for C trachomatis was used. The fourth child was being evaluated for sexually transmitted diseases after rape. Although the pediatrician sent a rectal culture to a large commercial laboratory it was later determined that the laboratory was using an enzyme immunoassay for culture confirmation leading to a false-positive result. At the least the use of these inappropriate tests resulted in unnecessary retesting and at the worst, unnecessary hospitalization, erroneous reports of sexual abuse and possibly unjustified prosecution and incarceration. Because of the social and legal implications it is important that practitioners be aware of these recommendations and require that commercial laboratories adhere to approved C trachomatis culture methods.

Adolescent↗

Activity of quinolones against Chlamydia pneumoniae.

Quinolones are currently being used as empirical therapy for the treatment of community-acquired pneumonia and other respiratory infections as they cover a broad range of conventional bacterial and 'atypical' pathogens, including Chlamydia pneumoniae. C. pneumoniae has been associated with 10 to 20% of community-acquired pneumonia in adults and recently has been implicated as being associated with several nonrespiratory conditions, including atherosclerosis. However, data on the treatment of even respiratory infection due to C. pneumoniae are limited. Although currently available quinolones have good activity against C. pneumoniae in vitro, all published treatment studies have relied on serological diagnosis, thus microbiological efficacy has not been assessed. Anecdotal experience suggests that in vitro activity may not always correlate with efficacy in vivo.

4-Quinolones↗

Antibody response to Chlamydia pneumoniae infection in children with respiratory illness.

Serologic diagnosis of Chlamydia pneumoniae infection has been based on the microimmunofluorescence test (MIF). However, recent prospective studies in children have found that >50% infected with C. pneumoniae failed to develop any antibodies detectable by MIF. In this study, single sera from 46 culture-positive and 42 culture-negative children with respiratory infection and known MIF status were examined by immunoblotting. Forty-one (89.1%) of the single sera from culture-positive and 27 (64.3%) from culture-negative children reacted to C. pneumoniae antigens in immunoblot. C. pneumoniae proteins most frequently recognized by sera from culture-positive patients were at 101-102, 72-76, 50-52, 48-49, 43-44, 41-42, and 30-31 kDa. However, there did not appear to be a correlation of specific band patterns and culture status.

Adolescent↗

Safety and efficacy of azithromycin in the treatment of community-acquired pneumonia in children.

OBJECTIVE: To compare the safety and efficacy of azithromycin with amoxicillin/clavulanate or erythromycin for the treatment of community-acquired pneumonia, including atypical pneumonia caused by Mycoplasma pneumoniae and Chlamydia pneumoniae. METHODS: Multicenter, parallel group, double blind trial in which patients 6 months to 16 years of age with community-acquired pneumonia were randomized 2:1 to receive either azithromycin for 5 days or conventional therapy for 10 days (amoxicillin/clavulanate if < or =5 years of age or erythromycin estolate if >5 years of age). Patients from 23 geographically diverse sites were evaluated for clinical outcomes and/or adverse events at Days 3 to 5, Days 15 to 19 and 4 to 6 weeks posttherapy. Microbiology (culture or polymerase chain reaction) was done at baseline and Days 15 to 19 for bacteria, Chlamydia pneumoniae and Mycoplasma pneumoniae. Serology for C. pneumoniae and M. pneumoniae was done at baseline and 4 to 6 weeks posttherapy. RESULTS: Of 456 patients enrolled during 17 consecutive months, 420 were evaluable. Clinical success at Study Days 15 to 19 was 94.6% in the azithromycin group and 96.2% in the comparative treatment group (P = 0.735) and at 4 to 6 weeks posttherapy 90.6 and 87.1%, respectively (P = 0.330). Evidence of infection was identified in 46% of 420 evaluable patients (1.9% bacteria, 29.5% M. pneumoniae and 15% C. pneumoniae). Microbiologic eradication was 81% for C. pneumoniae and 100% for M. pneumoniae in the azithromycin group vs. 100 and 57%, respectively, in the comparator group. Treatment-related adverse events occurred in 11.3% of the azithromycin group and 31% in the comparator group (P < 0.05). CONCLUSION: Azithromycin used once daily for 5 days produced a satisfactory therapeutic outcome similar to those of amoxicillin/clavulanate or erythromycin given three times a day for 10 days for treatment of community-acquired pneumonia. Azithromycin had significantly fewer side effects than comparator drugs.

Adolescent↗

Microbiologic efficacy of azithromycin and susceptibilities to azithromycin of isolates of Chlamydia pneumoniae from adults and children with community-acquired pneumonia.

Chlamydia pneumoniae was eradicated from the nasopharynges of 26 of 33 (78.8%) evaluable children and adults with community-acquired pneumonia who were treated with azithromycin. We tested 55 isolates of C. pneumoniae obtained from 46 of these patients against azithromycin. The MIC at which 90% of the isolates were inhibited and the minimal chlamydiacidal concentration at which 90% of strains tested were killed of azithromycin for these isolates were both 0.5 microg/ml. Seven patients remained culture positive after treatment. The MICs of azithromycin for isolates from two patients increased fourfold after therapy. However, all the patients with persistent infection improved clinically. Further studies of treatment of C. pneumoniae infection, utilizing culture, are needed both to assess efficacy and to monitor for the possible development of antibiotic resistance.

Adult↗

In vitro activity of a new 8-methoxyquinolone, BAY 12-8039, against Chlamydia pneumoniae.

The in vitro susceptibilities of 10 strains of Chlamydia pneumoniae to a new 8-methoxyquinolone, BAY 12-8039, and to ofloxacin, doxycycline, and erythromycin were determined. The activity of BAY 12-8039 was similar to that of ofloxacin, with a MIC at which 90% of the isolates had no inclusions and a minimal chlamydicidal concentration at which 90% of the isolates had no inclusions after passage of 1.0 microg/ml, but this activity was less than those of doxycycline and erythromycin.

Anti-Bacterial Agents↗