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Biomedical subjects

M R Hammerschlag

Publications and source records attributed to M R Hammerschlag.

At least 19 recordsLinked to original sources

In vitro activity of a novel diaminopyrimidine compound, iclaprim, against Chlamydia trachomatis and C. pneumoniae.

The in vitro activities of iclaprim, a novel dihydrofolate reductase inhibitor, azithromycin, and levofloxacin were tested against 10 strains of Chlamydia trachomatis and 10 isolates of Chlamydia pneumoniae. For C. trachomatis and C. pneumoniae, the iclaprim MIC and minimal bactericidal concentration at which 90% of isolates were inhibited (MIC(90) and MBC(90)) were 0.5 micro g/ml, compared to an azithromycin MIC(90) and MBC(90) of 0.125 micro g/ml and levofloxacin MIC(90)s and MBC(90)s of 1 micro g/ml for C. trachomatis and 0.5 micro g/ml for C. pneumoniae.

Anti-Bacterial Agents↗

Standardizing Chlamydia pneumoniae assays: recommendations from the Centers for Disease Control and Prevention (USA) and the Laboratory Centre for Disease Control (Canada).

Chlamydia pneumoniae has been associated with atherosclerosis and several other chronic diseases, but reports from different laboratories are highly variable and "gold standards" are lacking, which has led to calls for more standardized approaches to diagnostic testing. Using leading researchers in the field, we reviewed the available approaches to serological testing, culture, DNA amplification, and tissue diagnostics to make specific recommendations. With regard to serological testing, only use of microimmunofluorescence is recommended, standardized definitions for "acute infection" and "past exposure" are proposed, and the use of single immunoglobulin (Ig) G titers for determining acute infection and IgA for determining chronic infection are discouraged. Confirmation of a positive culture result requires propagation of the isolate or confirmation by use of polymerase chain reaction (PCR). Four of 18 PCR assays described in published reports met the proposed validation criteria. More consistent use of control antibodies and tissues and improvement in skill at identifying staining artifacts are necessary to avoid false-positive results of immunohistochemical staining. These standards should be applied in future investigations and periodically modified as indicated.

Bacteriological Techniques↗

Activity of telithromycin, a new ketolide antibacterial, against atypical and intracellular respiratory tract pathogens.

Atypical respiratory pathogens such as Mycoplasma pneumoniae and intracellular pathogens such as Legionella spp. and Chlamydia spp. form a significant proportion of the aetiological agents underlying community-acquired pneumonia (CAP). The clinical signs or radiological features of atypical pneumonia are generally insufficient to predict accurately the pathogen involved; in addition, high costs and a considerable length of time are involved in the identification of atypical pathogens. Treatment is, therefore, most often empirical, and it is important that the activity of antibacterial agents available to treat CAP is sufficiently broad to eradicate infection with both common and atypical bacterial pathogens. Telithromycin (HMR 3647) is the first of a new family of antibacterials, the ketolides, and has been designed specifically for the treatment of community-acquired respiratory tract infections (RTIs). The excellent activity of telithromycin against the respiratory tract bacterial pathogens most commonly associated with community-acquired RTIs, including resistant strains, is well established. This review examines the considerable body of evidence showing that telithromycin also has a high level of activity against atypical and intracellular respiratory tract bacterial pathogens.

Anti-Bacterial Agents↗

Mycoplasma pneumoniae infections.

Mycoplasma pneumoniae is a frequent cause of community-acquired respiratory infections in children and adults. Although the organism is felt to be the most frequent 'atypical' pathogen responsible for community-acquired pneumonia in adults, the prevalence of M. pneumoniae varies greatly from study to study, depending on the population and the diagnostic methods used. Recent studies have found the prevalence of M. pneumoniae in adults with pneumonia to range from 1.9 to over 30%. M. pneumoniae is also a frequent cause of outbreaks of respiratory disease in institutional settings. However, the diagnosis of M. pneumoniae infection is hampered by the lack of standardized, rapid, specific methods. This problem was illustrated by the results of an investigation of an outbreak of M. pneumoniae infection in a federal training facility. Accurate diagnosis required a combination of polymerase chain reaction and serology, as IgM antibodies were not present early in the course of the infection in many patients. Several papers evaluating various serological and polymerase chain reaction assays were published during the period of this review. An assessment of the actual performance of these tests was also hampered by the lack of standardized comparative methods. M. pneumoniae is susceptible in vitro to macrolides, tetracyclines and quinolone antibiotics; however, data are limited on the microbiological efficacy of these agents. Several pneumonia treatment studies were published during this period, practically all of them based the diagnosis of M. pneumoniae infection on serology; different methods and criteria were used in each study, and thus the microbiological efficacy could not be assessed. The Infectious Disease Society of America recently stated in their revised Practice Guidelines for the Management of Community-Acquired Pneumonia in Adults that, as there were no diagnostic tests available that reliably and rapidly detect M. pneumoniae, therapy must usually be empirical.

Adult↗

Ultrastructural study of Chlamydia pneumoniae in a continuous-infection model.

We have established an in vitro model of long-term continuous Chlamydia pneumoniae infection in HEp-2 cells. Using transmission electron microscopy, we demonstrated the presence of spontaneous abnormal chlamydial inclusions similar in appearance to the persistent chlamydial forms induced in vitro by treatment with cytokines or antibiotics or by nutrient deprivation.

Chlamydophila Infections↗

Is there an association between Kawasaki disease and Chlamydia pneumoniae?

The clinical and epidemiological features of Kawasaki disease (KD) are consistent with an infectious cause. Because chronic infection with Chlamydia pneumoniae has been implicated in the pathogenesis of atherosclerosis, it has been suggested that it may also be involved in the pathogenesis of KD. Paired sera (baseline pretreatment and 1 year after treatment with intravenous immunoglobulin [IVIG]) from 26 children with KD and 29 age-matched controls were examined by microimmunofluorescence (MIF) serology and immunoblotting. There were no significant differences in the prevalence of anti-C. pneumoniae IgG, IgA, or IgM between cases and controls; however, 73%-85% of sera from cases and controls reacted with C. pneumoniae proteins by immunoblotting. There was significantly more reactivity in the pre-IVIG, but not post-IVIG, KD sera compared with sera from controls to proteins at 72-74 kDa and 74-76 kDa. They may be heat shock proteins. The results of this study do not support an association between KD and C. pneumoniae on the basis of MIF and immunoblot analysis.

Adolescent↗

Microbiologic efficacy of moxifloxacin for the treatment of community-acquired pneumonia due to Chlamydia pneumoniae.

Nasopharyngeal specimens for culture of Chlamydia pneumoniae were obtained from patients participating in two pneumonia treatment studies: an open study of 400 mg moxifloxacin orally, qds for 10 days and a randomized, double-blind comparison of moxifloxacin, 400 mg orally, qds versus clarithromycin, 500 mg orally, bd, both for 10 days. C. pneumoniae was eradicated from the nasopharynx of seven of ten (70%) microbiologically evaluable patients who were treated with moxifloxacin and four of four who were treated with clarithromycin. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of 21 isolates of C. pneumoniae from 18 patients obtained before and after therapy were performed against moxifloxacin and clarithromycin. The MIC(90)s and MBC(90)s for moxifloxacin and clarithromycin were 1 and 0.06 mg/l, respectively. The MICs and MBCs against moxifloxacin of six isolates from three persistently infected patients who were treated with the drug were the same at baseline and follow-up. The persistence of C. pneumoniae after treatment with moxifloxacin was probably not due to the emergence of resistance.

Administration, Oral↗

In vitro activity of GAR-936 against Chlamydia pneumoniae and Chlamydia trachomatis.

We evaluated the in vitro activity of GAR-936, a novel glycylcycline antibiotic, against ten isolates of Chlamydia pneumoniae and five strains of C. trachomatis. Susceptibility testing was done in HEp-2 cells. The MIC90s and MBC90s of GAR-936, doxycycline, ofloxacin and clarithromycin against C. pneumoniae were 0.125, 0.25, 0.25 and 0.06 mg/l, respectively. The MICs and MBCs of GAR-936, doxycycline, ofloxacin and clarithromycin against C. trachomatis were 0.03-0.125, 0.25, 0.25-0.5 and 0.06 mg/l, respectively. GAR-936 had excellent activity against both chlamydial species and may have a potential role in the treatment of human chlamydial infection.

Adult↗

Activity of gemifloxacin and other new quinolones against Chlamydia pneumoniae: a review.

Quinolones are currently used as empirical therapy for treatment of community-acquired lower respiratory infections as they are effective against a broad range of conventional bacterial and 'atypical' pathogens, including Chlamydia pneumoniae. C. pneumoniae is estimated to be associated with 10-20% of community-acquired pneumonia in adults, and has recently been suggested to play a role in several non-respiratory conditions, including atherosclerosis. The newer, third-generation quinolones have enhanced activity against Gram-positive bacteria, including Streptococcus pneumoniae, and prolonged serum half-lives that permit once-daily dosing. Although gemifloxacin (SB-265805) and other new quinolones have good activity against C. pneumoniae in vitro, practically all published treatment studies have relied on serological diagnosis. Consequently, the microbiological efficacy of these agents in human infection has not been assessed. This paper reviews what is known to date of the in vivo microbiological efficacy of the quinolones against C. pneumoniae, and demonstrates the importance of assessing this parameter when evaluating the clinical utility of these agents in C. pneumoniae infection.

Adult↗

In vitro activity of ABT 773, a new ketolide antibiotic, against Chlamydia pneumoniae.

The in vitro activities of ABT 773, telithromycin (HMR 3647), azithromycin, clarithromycin, erythromycin, and levofloxacin were tested against 20 strains of Chlamydia pneumoniae. The MIC at which 90% of the isolates were inhibited and the minimal bactericidal concentration at which 90% of the isolates were killed by ABT 773 were 0.015 microg/ml (range, 0.008 to 0.015 microg/ml). ABT 773 was the most active antibiotic tested in this study.

Chlamydia Infections↗