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Biomedical subjects

Margaret R Hammerschlag

Publications and source records attributed to Margaret R Hammerschlag.

At least 19 recordsLinked to original sources

Isolation and antimicrobial susceptibilities of Chlamydial isolates from Western barred bandicoots.

A range of species of Chlamydiales have previously been detected in a variety of Australian marsupials, including koalas and western barred bandicoots. Thirty-seven ocular, urogenital, or nasal swabs were obtained from 21 wild western barred bandicoots. Chlamydia culture and antibiotic susceptibility testing were performed for cycloheximide-treated HEp-2 cells in 96-well microtiter plates. Chlamydia spp. were isolated from 11 specimens from 9 (42.8%) bandicoots. All isolates were identified as Chlamydiales by conventional PCR with 16S and 23S rRNA gene primers specific to Chlamydiales and were confirmed to be Chlamydia pneumoniae by a C. pneumoniae-specific ompA-based real-time PCR assay and 16S rRNA and 23S rRNA gene signature sequence analyses. The MICs of azithromycin, doxycycline, ciprofloxacin, and enrofloxacin for 10 C. pneumoniae isolates from these bandicoots ranged from 0.015 to 1 microg/ml, 0.25 to 1 microg/ml, 0.25 to 2 microg/ml, and 0.25 to 0.5 microg/ml, respectively. The MICs at which 90% of isolates were inhibited and the minimal bactericidal concentrations were within the ranges reported previously for human isolates of C. pneumoniae.

Animals↗

Infection with Simkania negevensis in Brooklyn, New York.

BACKGROUND: Simkania negevensis is a Chlamydia-like intracellular organism that is prevalent in populations from a wide range of geographic areas. The role of the organism in respiratory disease in the United States is unknown. OBJECTIVE: To study the association between infection with S. negevensis and bronchiolitis, pneumonia or asthma in Brooklyn, New York. MATERIALS AND METHODS: Pediatric and adult inpatients/outpatients with bronchiolitis, pneumonia or asthma were recruited, and a similar number of healthy control subjects were enrolled. Nasopharyngeal swabs were obtained for culture of S. negevensis and Chlamydia pneumoniae and polymerase chain reaction detection of S. negevensis. Sera were obtained for measurement of antibodies to S. negevensis and C. pneumoniae. RESULTS: One hundred eighty-eight patients and 110 healthy control subjects were enrolled. S. negevensis serologic assays were positive for 18% of patients, compared with 29% of control subjects (P = 0.09). S. negevensis DNA was detected by PCR for 17% of case subjects and 23% of control subjects (P = 0.25). S. negevensis was isolated by culture for 1 patient with bronchiolitis. C. pneumoniae IgG and S. negevensis IgG were found to increase with increasing age, ie, 14%, 50% and 78% (C. pneumoniae) and 13%, 17% and 33% (S. negevensis) for subjects 0-18 months, 18 months-18 years and older than 18 years of age, respectively. CONCLUSION: S. negevensis was not a significant respiratory pathogen in Brooklyn, NY, during the period of the study.

Adolescent↗

Emergence of resistance to rifampin and rifalazil in Chlamydophila pneumoniae and Chlamydia trachomatis.

Although rifamycins have excellent activity against Chlamydophila pneumoniae and Chlamydia trachomatis in vitro, concerns about the possible development of resistance during therapy have discouraged their use for treatment of chlamydial infections. Rifalazil, a new semisynthetic rifamycin with a long half-life, is the most active antimicrobial against C. pneumoniae and C. trachomatis in vitro, indicating its potential for treatment of acute and chronic C. pneumoniae and C. trachomatis infections. We investigated the effect of serial passage of two C. pneumoniae isolates and two serotypes of C. trachomatis in subinhibitory concentrations of rifalazil and rifampin on the development of phenotypic and genotypic resistance. C. trachomatis developed resistance to both antimicrobials within six passages, with higher level resistance to rifampin (128 to 256 microg/ml) and lower level resistance to rifalazil (0.5 to 1 microg/ml). C. pneumoniae TW-183 developed only low-level resistance to rifampin (0.25 microg/ml) and rifalazil (0.016 microg/ml) after 12 passages. C. pneumoniae CWL-029 failed to develop resistance to either drug. Two unique mutations emerged in the rpoB gene of rifampin (L456I) and rifalazil (D461E)-resistant C. pneumoniae TW-183. A single mutation (H471Y) was detected in both rifampin- and rifalazil-resistant C. trachomatis UW-3/Cx/D, and a unique mutation (V136F) was found in rifalazil-resistant BU-434/L(2). No mutations were detected in the entire rpoB gene of rifampin-resistant BU-434/L(2). This is the first description of antibiotic resistance-associated mutations in C. pneumoniae and of rifampin resistance in C. trachomatis not associated with mutations in the rpoB gene.

Base Sequence↗

Therapeutic approaches to Chlamydia infections.

Chlamydia trachomatis ocular and urogenital infections represent major public health problems, whereas Chlamydophila pneumoniae is a common aetiological agent of community-acquired pneumonia. The obligate intracellular lifestyle of these established pathogens poses challenges to both their diagnosis and treatment. Tetracyclines, macrolides and quinolones remain the antimicrobials of choice for the treatment of infections due to Chlamydiaceae.

Anti-Bacterial Agents↗

Genetic and culture-based approaches for detecting macrolide resistance in Chlamydia pneumoniae.

Three clinical Chlamydia pneumoniae isolates for which the MIC of azithromycin increased after treatment were investigated for genetic evidence of macrolide resistance. Attempts to induce antibiotic resistance in vitro were made. No genetic mechanism was identified for the phenotypic change in these C. pneumoniae isolates. No macrolide resistance was obtained in vitro.

Anti-Bacterial Agents↗

Is Chlamydia pneumoniae infection associated with stroke in children with sickle cell disease?

BACKGROUND: Stroke is often a devastating complication of sickle cell disease (SCD). Most children with SCD-related stroke have stenotic and occlusive disease of cerebral blood vessels due to intimal hyperplasia. This hyperplasia is hypothesized to result from an inflammatory response similar to that in atherosclerosis and has been attributed to infection by Chlamydia pneumoniae. OBJECTIVE: To determine whether C pneumoniae infection is associated with stroke and cerebrovascular disease, including transient ischemic attacks and abnormal transcranial Doppler examinations, in children with SCD. METHODS: Children with SCD on chronic transfusion due to a history of stroke, transient ischemic attack, or abnormal transcranial Doppler; children with SCD without stroke; healthy controls; and children being transfused for other reasons were enrolled. Peripheral blood and nasopharyngeal (NP) swab specimens were collected from all patients. In patients on transfusion, pretransfusion specimens and samples from the unit of packed red blood cells being transfused were obtained. Peripheral blood monocytic cells (PBMCs) and NP swab specimens were cultured for C pneumoniae in HEp-2 cells. C pneumoniae polymerase chain reaction was performed on PBMCs with a nested touch-down method with primers from the omp-1gene (in duplicate) and a second real-time polymerase chain reaction by using 16S ribosomal RNA primers. RESULTS: C pneumoniae DNA was detected in the PBMCs of 1 of 14 (7.1%) children with SCD on chronic transfusion, 1 of 10 (10%) sickle cell controls, 1 of 10 (10%) healthy controls, and none of the 5 children receiving chronic transfusion for other reasons. It was not detected in specimens from transfusion units. One child with SCD and stroke, 1 sickle cell control, and 1 transfusion control had positive NP cultures for C pneumoniae. C pneumoniae DNA was not detected in their PBMCs, and all 3 children were asymptomatic. C pneumoniae was not detected by culture of PBMCs from any of the patients after 7 passages. CONCLUSION: Stroke in children with SCD does not seem to be associated with C pneumoniae infection in our population.

Adolescent↗

Microbiological efficacy of ABT-773 (cethromycin) for the treatment of community-acquired pneumonia due to Chlamydia pneumoniae.

Nasopharyngeal specimens for culture of Chlamydia pneumoniae were obtained from patients with community-acquired pneumonia enrolled in a randomized study comparing the novel ketolide antibiotic ABT-773 at a dose of 150 mg once a day to 150 mg twice a day, by mouth for 10 days. C. pneumoniae was eradicated from the nasopharynx of 10 of 10 (100%) microbiologically evaluable patients. MICs and MBCs for 13 isolates of C. pneumoniae from 12 patients obtained before and after therapy were performed against ABT-773. The MIC90 and MBC90 of ABT-773 were 0.015 mg/L.

Adult↗

The role of Chlamydia pneumoniae infection in children with chronic sinusitis.

BACKGROUND: Chlamydia pneumoniae infection is a frequent cause of lower respiratory disease in both adults and children. However, its role in upper respiratory disease, including sinusitis, is less clear. OBJECTIVE: To determine the role of infection with C. pneumoniae in chronic sinusitis in children. DESIGN: Prospective collection of specimens. SETTING: Tertiary care academic medical center. PARTICIPANTS: Children with clinical and radiologic evidence of chronic sinusitis unresponsive to medical management undergoing adenoidectomy, maxillary sinus lavage, or endoscopic sinus surgery for treatment. Intervention Nasopharyngeal and middle meatal swabs and portions of surgical specimens were obtained and cultured for C. pneumoniae. RESULTS: Specimens were obtained from 20 children (14 boys and 6 girls) aged 3 through 16 years. Thirteen bilateral endoscopic ethmoidectomies with maxillary antrostomies, 10 adenoidectomies, and 3 bilateral maxillary sinus lavages were performed. Chlamydia pneumoniae was isolated from the nasopharyngeal swab and adenoid tissue of 1 child (aged 6 years); however, his middle meatal swabs and maxillary sinus aspirates were negative. After 10 days of treatment with clarithromycin, repeat nasopharyngeal cultures were negative for C. pneumoniae. CONCLUSIONS: With the use of sensitive culture methods, C. pneumoniae was not isolated from sinus specimens of children enrolled in this study. This preliminary study suggests that C. pneumoniae does not play a significant role in chronic sinusitis in children.

Adolescent↗

Pneumonia due to Chlamydia pneumoniae in children: epidemiology, diagnosis, and treatment.

The term "atypical" pneumonia has been used to differentiate infections caused by Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella, and other related organisms from pneumonia caused by classic bacteria, the prototype being Streptococcus pneumoniae. However, recent studies demonstrated that the clinical presentation of pneumonia due to atypical pathogens cannot readily be differentiated from those caused by "typical" bacteria. This is further complicated by the observation that coinfections with atypical pathogens and other bacteria are frequent. Nonetheless, the term "atypical" can be useful, as these organisms share a number of characteristics that separate them from "typical" bacteria. They are either obligate or facultative intracellular parasites that cannot be isolated using routine microbiologic methods. The most commonly used method of diagnosis of these infections is serology, which has significant limitations. Although C. pneumoniae is now recognized worldwide as a common cause of respiratory infections in adults and children, major gaps remain in our knowledge of the biology of this organism and how it causes disease, in major part due to the lack of readily available, standardized diagnostic methods.

Adolescent↗

Differential expression of genes encoding membrane proteins between acute and continuous Chlamydia pneumoniae infections.

Chlamydia pneumoniae is associated with several chronic human diseases, including chronic obstructive pulmonary disease and atherosclerotic cardiovascular disease. During chronic disease, organisms are believed to exist in a persistent phase that is not well understood at the genetic level. Long-term in vitro continuous infections are spontaneously persistent and are less susceptible than in vitro acute infections to treatment with antibiotics, and are therefore particularly relevant as an in vitro model of in vivo chronic disease. Real-time reverse transcriptase-PCR (r-t RT-PCR) was used to quantitate transcript copy numbers of 13 genes in continuous and acute infections with C. pneumoniae. The set of genes studied encodes proteins with known or predicted functions in the cell membrane, the inclusion membrane, cell division, metabolism, and immunopathology. Significant upregulation was seen for five genes (CPn0483, nlpD, ompA, pmp1 and porB) in continuous cultures. The genes omcB, pmp1, and porB, all of which encode membrane proteins, shared similar patterns of expression over both acute and continuous profiles. These results show that Chlamydia in the long-term continuous model of persistence have a unique transcription profile, adding to our knowledge of regulation of this important stage of chlamydial growth.

Acute Disease↗