Susceptibilities to clarithromycin and erythromycin of isolates of Chlamydia pneumoniae from children with pneumonia

Abstract

We tested in vitro 49 isolates of Chlamydia pneumoniae obtained from 35 children with community-acquired pneumonia against clarithromycin and erythromycin. The children were part of a treatment study comparing the two drugs. Clarithromycin was 2-to 10-fold more active than erythromycin, with a MIC for 90%6 of strains tested and minimal chlamydiacidal concentration for 90%Yo of strains tested of 0.031 ,ig/ml compared with 0.125 ,ug/ml for erythromycin. Eight of these children, two of whom were treated with erythromycin and six of whom received clarithromycin, remained culture positive after treatment. We were able to test 21 isolates from these children. All were susceptible to both drugs, and the MICs did not change after therapy.Chlamydia pneumoniae is emerging as a frequent cause of community-acquired respiratory tract infection in adults and children, including pneumonia and bronchitis (3, 4, 7). There are limited data on the treatment of these infections, because most studies have used serology only, and thus microbiologic efficacy could not be assessed. As part of a nationwide, multicenter study comparing clarithromycin and erythromycin suspensions for the treatment of community-acquired pneumonia in children 3 through 12 years of age, we isolated C. pneumoniae from 42 (16%) of the 260 children enrolled (7). Although all of the children with C. pneumoniae infection improved clinically and radiographically, 9 (21%) of these children remained culture positive after treatment. C. pneumoniae was eradicated from 15 of 19 (79%) evaluable patients who were treated with clarithromycin and 12 of 14 (86%) of those treated with erythromycin. The dosages of clarithromycin and erythromycin suspensions were 15 and 40 mg/kg of body weight per day, respectively, both given in two divided doses for 10 days. We performed in vitro susceptibility testing against clarithromycin and erythromycin with isolates of C. pneumoniae from these children. MATERIALS AND METHODSClarithromycin (Abbott Laboratories, North Chicago, Ill.) and erythromycin (Eli Lilly and Co., Indianapolis, Ind.) were supplied as powders and solubilized according to the instructions of the manufacturers.The C. pneumoniae isolates were originally isolated from nasopharyngeal swab specimens cultured in cycloheximidetreated HEp-2 cells (1). Patient isolates were passed three to four times in tissue culture in antibiotic-free medium.Susceptibility testing of C. pneumoniae was performed with cell culture of HEp-2 cells grown in 96-well microtiter plates (6). Each well was inoculated with 0.2 ml of the organism diluted to yield 103 inclusion-forming units/ml and centrifuged at 2,000 x g for 1 h. The wells were then aspirated and overlayed with 0. and serial twofold dilutions of the test drug. After incubation at 35°C for 72 h, cultures were fixed and stained for inclusions with fluorescein-conjugated antibody to the lipopolysaccharide genus antigen (Pathfinder Chlamydia Culture Confirmation System; Kallestad Diagnostics, Chaska, Minn.).The MIC was the lowest antibioti...

Chlamydia pneumoniae and Atherosclerosis: Critical Assessment of Diagnostic Methods and Relevance to Treatment Studies

“…All these children improved clinically despite persistence of the organism. Persistence did not appear to be related to the development of antibiotic resistance since all the isolates remained susceptible to erythromycin and clarithromycin during and after treatment (119). The experience with azithromycin has been similar.…”

“…pneumoniae is susceptible in vitro to a wide range of antimicrobial agents, including macrolides, tetracyclines, and quinolones, that target either protein or DNA synthesis (Table 6) (39,52,53,54,119,120,121). Recently, Gieffers et al (39) reported that the in vitro susceptibilities of five isolates of C. pneumoniae cultured from vascular tissue did not differ significantly from those of respiratory isolates.…”

Chlamydia pneumoniae and the lung

“…All of these children improved clinically despite persistence of the organism. Persistence was not related to the development of antibiotic resistance as all isolates remained susceptible to erythromycin and clarithromycin during and after treatment [51]. Clarithromycin is 10±100-fold more active than erythromycin in vitro and has superior pharmacokinetics and tissue penetration, and yet was not more effective than erythromycin in eradicating C. pneumoniae from the respiratory tract.…”

Importance of acute Mycoplasma pneumoniae and Chlamydia pneumoniae infections in children with wheezing

“…The standard treatment with steroids and bronchodilators was equivalent in clarithromycin-treated and nonantibiotictreated children as regards the drugs used and the length of therapy. Clarithromycin was chosen based on the in vitro susceptibility to macrolides of M. pneumoniae and C. pneumoniae [13,14]. The duration of therapy was based on previous clinical observations from use of this antibiotic in children [15,16].…”