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M R Hammerschlag

Publications and source records attributed to M R Hammerschlag.

At least 19 recordsLinked to original sources

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 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

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

In vitro activity of a new ketolide antibiotic, HMR 3647, against Chlamydia pneumoniae.

The in vitro activities of HMR 3647, roxithromycin, erythromycin, and azithromycin against 19 strains of Chlamydia pneumoniae were tested. The MIC at which 90% of the isolates are inhibited and the minimum bactericidal concentration at which 90% of the isolates are killed of HMR 3647 were 0.25 microgram/ml (range, 0.015 to 2 micrograms/ml). Nine recently obtained clinical isolates from children with pneumonia were more susceptible (MICs, 0.015 to 0.0625 microgram/ml) than older strains that had been passaged more extensively.

Anti-Bacterial Agents

Sexually transmitted diseases in sexually abused children: medical and legal implications.

Sexually transmitted diseases (STDs) may be transmitted during sexual assault. In children, the isolation of a sexually transmitted organism may be the first indication that abuse has occurred. Although the presence of a sexually transmissible agent from a child beyond the neonatal period is suggestive of sexual abuse, exceptions do exist. In this review I discuss the issues of the transmissibility and diagnosis of STDs in the context of child sexual abuse. Rectal or genital infection with Chlamydia trachomatis among young children may be the result of perinatally acquired infection and may persist for as long as 3 years. A major problem with chlamydia testing in the context of suspected sexual abuse in children has been the inappropriate use of non-culture tests. Although the new generation of nucleic acid amplification tests have shown high sensitivity and specificity with genital specimens from adults, data on use of these tests on any site in children are practically non-existent. Bacterial vaginosis (BV) has been identified among children who have been abused and among those who have not been abused. However, many of the methods used to diagnose BV in adults have not been evaluated in children. Recent studies of perinatal infection with human papillomavirus (HPV) have been inconclusive. HPV DNA has been detected at various sites in children who have not been abused. The relation to the development of clinically apparent genital warts is unclear. Although HIV can be acquired through sexual abuse in children, the exact risk to the child and which children should be screened is still controversial.

Child

In-vitro activity of dirithromycin against Chlamydia pneumoniae.

The in-vitro susceptibilities of 12 strains of Chlamydia pneumoniae were determined for dirithromycin, a new macrolide antibiotic, erythromycyclamine, its active metabolite, and erythromycin. Both dirithromycin and erythromycyclamine had an MIC90 of 2 mg/L, as compared with 0.062 mg/L for erythromycin. The combination of dirithromycin and erythromycyclamine appeared to be additive. Determination of the role of dirithromycin for the treatment of C. pneumoniae infection will depend on the results of prospective, controlled studies utilizing culture.

Anti-Bacterial Agents

Use of polymerase chain reaction for the detection of Chlamydia trachomatis in ocular and nasopharyngeal specimens from infants with conjunctivitis.

BACKGROUND: Chlamydia trachomatis is the most common identifiable infectious cause of neonatal conjunctivitis. Nonculture tests including enzyme immunoassays and direct fluorescent antibody tests have been shown to perform well for the diagnosis of chlamydial conjunctivitis with sensitivities and specificities > or = 90%. However, the performance with respiratory specimens has been less than satisfactory. METHODS: We compared a new, commercially available polymerase chain reaction (PCR) assay, Roche AMPLICOR (Roche Diagnostic Systems, Branchburg, NJ) with culture for the detection of C. trachomatis in conjunctival and nasopharyngeal specimens from infants with conjunctivitis. We also evaluated AMPLICOR for the detection of C. trachomatis in the urine of mothers of positive infants. RESULTS: Ocular and nasopharyngeal specimens from 75 infants with conjunctivitis were obtained for culture and PCR. AMPLICOR was equivalent to culture for eye specimens and more sensitive than culture for nasopharyngeal specimens. The sensitivity, specificity and positive and negative predictive values of PCR compared with culture for conjunctival specimens were 92.3, 100, 100 and 98.4%, respectively. The sensitivity, specificity and positive and negative predictive values for nasopharyngeal specimens were 100, 97.2, 60 and 100%, respectively. We also detected C. trachomatis by PCR in the urine of 12 mothers of culture positive infants. CONCLUSIONS: PCR performed comparably to culture for detection of C. trachomatis in conjunctival and nasopharyngeal specimens from infants with conjunctivitis.

Bacteriological Techniques

Chlamydia pneumoniae in acute otitis media.

BACKGROUND: Aerobic bacterial pathogens are recovered from 65 to 85% of patients with acute otitis media (AOM). Although Chlamydia pneumoniae is a common pathogen of pediatric pneumonia, it has rarely been cultured from children with chronic otitis media and its role in AOM is unknown. METHODS: We cultured for C. pneumoniae in tympanocentesis aspirates and nasopharyngeal swabs from 101 consecutive, otherwise healthy children with AOM or refractory AOM. A control group of 50 similarly aged, healthy children was evaluated for nasopharyngeal carriage of C. pneumoniae. Specimens were also evaluated by PCR for C. pneumoniae. RESULTS: C. pneumoniae was recovered by tympanocentesis in 8 (8%) of 101 children with AOM. Among the 8 children with C. pneumoniae-positive-AOM, 5 had C. pneumoniae detected by PCR in middle ear fluid, none had C. pneumoniae recovered by nasopharyngeal culture or PCR and 5 were younger than 16 months. C. pneumoniae was the sole pathogen isolated in 2 patients. Copathogens included beta-lactamase-positive positive Haemophilus influenzae (2), beta-lactamase positive Moraxella catarrhalis (1), penicillin-resistant Streptococcus pneumoniae (2) and penicillin-susceptible S. pneumoniae (1). C. pneumoniae was recovered from nasopharyngeal culture in 2 additional patients with C. pneumoniae-negative AOM and in none of 50 healthy control children, although 2 controls were positive by PCR from the nasopharynx. CONCLUSIONS: This is the first study to report the isolation of C. pneumoniae in middle ear fluid of children with AOM.

Acute Disease

In vitro activity of trovafloxacin against Chlamydia pneumoniae.

The in vitro susceptibilities of 12 strains of Chlamydia pneumoniae to a new quinolone, trovafloxacin, and ofloxacin, doxycycline, erythromycin, and azithromycin were determined. The activity of trovafloxacin was similar to that of ofloxacin, with a MIC at which 90% of the isolates are inhibited and a minimal concentration at which 90% of the isolates are killed of 1.0 microg/ml, but trovafloxacin was less active than doxycycline, erythromycin, and azithromycin.

Anti-Bacterial Agents

Evaluation of Chlamydia immunoglobulin M (IgM), IgG, and IgA rELISAs Medac for diagnosis of Chlamydia pneumoniae infection.

Chlamydia pneumoniae is an important pathogen responsible for a variety of respiratory diseases in humans. Cell culture remains the most specific method for C. pneumoniae diagnosis, but it is labor-intensive and time-consuming. Thus, serology, particularly microimmunofluorescence (MIF) testing, is frequently utilized. However, the MIF test has a significant subjective component. We evaluated a new serological test: Chlamydia Immunoglobulin M (IgG, IgA, and IgM rELISAs Medac, based on a recombinant Chlamydia-specific lipopolysaccharide (LPS) fragment, for the diagnosis of C. pneumoniae infection. The results of this study demonstrated that the use of rELISAs Medac with single sera does not appear to be sensitive or specific for diagnosis of C. pneumoniae infection compared to culture. In children, sensitivities of the rELISAs compared to culture did not exceed 34.2%, and the specificities ranged from 68.4% (IgG) to 91.2% (IgA). In adults, the sensitivities of the rELISAs were slightly higher, up to 77.8% (IgA or IgG), but the specificities ranged from a very low 20.8% for IgA or IgG to 81.1% for IgM. When multiple sera were tested, the results of the rELISAs Medac correlated with culture results in five of eight (62.5%) patients. However, this offers only a retrospective diagnosis, which makes it difficult to manage these patients prospectively.

Adolescent

Evaluation of a new optical immunoassay for diagnosis of neonatal chlamydial conjunctivitis.

The BioStar OIA Chlamydia test (BioStar, Inc., Boulder, Colo.) is a novel immunoassay system that uses changes in reflection of light to directly detect chlamydial antigen in clinical specimens. We compared the optical immunoassay (OIA) with culture for detecting Chlamydia trachomatis in ocular specimens from infants with suspected chlamydial conjunctivitis. We initially performed a retrospective evaluation, testing 152 ocular specimens previously collected for culture with the OIA. The sensitivity and specificity were 94.2 and 97%, respectively. A subsequent prospective study evaluating 37 ocular specimens from infants with suspected C. trachomatis conjunctivitis revealed a sensitivity and specificity of 100 and 92.6%, respectively.

Antigens, Bacterial

Chlamydia pneumoniae infection in patients with cystic fibrosis.

The prevalence of atypical community-acquired infections as acute pulmonary exacerbations in patients with cystic fibrosis was prospectively studied. Thirty-two patients admitted to the hospital because of acute pulmonary exacerbations and 24 clinically stable patients seen for their routine visits were examined. The prevalence of infection with Chlamydia pneumoniae was assessed by culture and serology, and the presence of IgE to C. pneumoniae was studied by immunoblotting. A subgroup of patients was also examined for the presence of Mycoplasma pneumoniae infection. C. pneumoniae was isolated from four patients presenting with acute pulmonary exacerbations (12.5%) and from none of the stable patients; all patients for whom cultures were positive also had IgE to C. pneumoniae. Polymerase chain reaction analysis for M. pneumoniae was not positive for any patient, and only one patient with an acute exacerbation had an antibody titer compatible with a recent infection. We conclude that infection with C. pneumoniae is associated with acute pulmonary exacerbations in some patients with cystic fibrosis and that it may trigger the production of IgE specific to C. pneumoniae, thus leading to bronchial reactivity in these patients.

Adolescent