Comparison of the effects of macrolides, amoxicillin, ceftriaxone, doxycycline, tobramycin and fluoroquinolones, on the production of pneumolysin by Streptococcus pneumoniae in vitro (original) (raw)
Related papers
macrolide-susceptible and-resistant Streptococcus pneumoniae
2015
Background: The association between macrolide resistance mechanisms and bacteriological eradication of Streptococcus pneumoniae remains poorly studied. The present study, using an in vitro pharmacodynamic model, assessed azithromycin activity against macrolide-susceptible and-resistant S. pneumoniae simulating clinically achievable free serum (S), epithelial lining fluid (ELF) and middle ear fluid (MEF) concentrations. Materials and methods: Two macrolide-susceptible [PCR-negative for both mef(A) and erm(B)] and six macrolide-resistant [five mef(A)-positive/erm(B)-negative displaying various degrees of macrolide resistance and one mef(A)-negative/erm(B)-positive] S. pneumoniae were tested. Azithromycin was modelled simulating a dosage of 500 mg/250 mg by mouth, once a day [free S: maximum concentration (C max) 0.2 mg/L, t 1/2 68 h; free ELF C max 1.0 mg/L, t 1/2 68 h] and 10 mg/kg by mouth, once a day (free MEF: C max 1.0 mg/L, t 1/2 68 h) using a one compartment model. Starting inocula were 1 × 10 6 cfu/mL in Mueller-Hinton broth with 2% lysed horse blood. Sampling at 0, 2, 4, 6, 12, 24 and 48 h assessed the extent of bacterial killing (decrease in log 10 cfu/mL versus initial inoculum). Results: Free azithromycin concentrations in serum, ELF and MEF simulating time above the MIC (T > MIC) of 100% [area under the curve to MIC (AUC 0-24 /MIC] ≥ 36.7] were bactericidal (≥3 log 10 killing) at 24 and 48 h versus macrolide-susceptible S. pneumoniae. Against macrolide-resistant S. pneumoniae, free serum concentrations providing T > MIC of 0% or AUC 0-24 /MIC ≤ 1.1 demonstrated no bacterial inhibition followed by regrowth at 24 and 48 h, whereas free ELF and MEF providing T > MIC of 0% or AUC 0-24 /MIC of 4.6 produced a bacteriostatic (0.2-0.5 log 10 killing at 24 h) effect with a mef(A) strain with an azithromycin MIC of 2 mg/L. Against mef(A)-positive S. pneumoniae strains with azithromycin MICs ≥ 4 mg/L, no bacterial killing occurred at any time point and rapid regrowth was observed simulating ELF or MEF T > MIC of 0% or AUC 0-24 /MIC ≤ 2.3. Conclusion: Azithromycin serum, ELF and MEF concentrations rapidly eradicated macrolide-susceptible S. pneumoniae but did not eradicate macrolide-resistant S. pneumoniae regardless of resistance phenotype.
Clinical Infectious Diseases, 2002
The rate of macrolide resistance among Streptococcus pneumoniae is increasing, but some investigators have questioned its clinical relevance. We conducted a matched case-control study of patients with bacteremic pneumococcal infection at 4 hospitals to determine whether development of breakthrough bacteremia during macrolide treatment was related to macrolide susceptibility of the pneumococcal isolate. Case patients (n p ) were patients who had pneumococcal bacteremia and an isolate that was either resistant or intermediately 86 resistant to erythromycin. Controls ( ) were patients matched for age, sex, location, and year that n p 141 bacteremia developed who had an erythromycin-susceptible pneumococcus isolated. Excluding patients with meningitis, 18 (24%) of 76 case patients and none of 136 matched controls were taking a macrolide when blood was obtained for culture ( ). Moreover, 5 (24%) of 21 case patients with the low-P p .00000012 level-resistant M phenotype and none of 40 controls were taking a macrolide ( ). These data show P p .00157 that development of breakthrough bacteremia during macrolide or azalide therapy is more likely to occur among patients infected with an erythromycin-resistant pneumococcus, and they also indicate that in vitro macrolide resistance resulting from both the efflux and methylase mechanisms is clinically relevant.
The clinical impact of macrolide resistance in pneumococcal respiratory infections
International Journal of Antimicrobial Agents, 2001
By the 1960s, several reports of bacteria with reduced susceptibility to antibiotics were published. In recent years, the problem of antibiotic resistance has magnified. In the treatment of respiratory tract infections, the development of resistance is of particular concern; 67% of antibiotic use in adults and 87% in children is for the treatment of such infections. Streptococcus pneumoniae is the most common cause of community-acquired pneumonia and is a frequently isolated bacterial species in patients with other respiratory tract infections. Increasing levels of resistance may have important implications in the clinical setting. Physicians need to consider local susceptibility data, in addition to the pharmacokinetic and pharmacodynamic features of compounds, when selecting appropriate antibiotics for the treatment of bacterial infections.
Antimicrobial Agents and Chemotherapy, 2006
The connection between regional rates of antimicrobial resistance in Streptococcus pneumoniae and regional antimicrobial use in Finland was investigated. During the 6-year study period of 1997 to 2002, a total of 31,609 S. pneumoniae isolates were tested for penicillin resistance and a total of 23,769 isolates were tested for macrolide resistance in 18 central hospital districts in Finland. The regional macrolide resistance rates were compared with the local use of (i) all macrolides pooled and (ii) azithromycin. The penicillin resistance levels were compared with the consumption data for (i) penicillins, (ii) cephalosporins, (iii) all beta-lactams pooled, and (iv) all macrolides pooled. A statistically significant association between macrolide resistance and total use of macrolides and the use of azithromycin was found. Moreover, total use of beta-lactams and total use of cephalosporins were significantly connected to low-level penicillin resistance. A statistically significant association between penicillin-nonsusceptible isolates and penicillin or total macrolide consumption was not found. In conclusion, total macrolide use and azithromycin use are associated with increased macrolide resistance, and beta-lactam use and cephalosporin use are connected to increased low-level penicillin resistance in S. pneumoniae. Unnecessary prescribing of macrolides and cephalosporins should be avoided.
The Medical journal of Malaysia
The in vitro activities of 6 antimicrobial agents against clinical isolates of Streptococcus pneumoniae (pneumococci) were investigated and the erythromycin minimum inhibitory concentrations (MICs) were correlated with the two major macrolide resistance determinants, mef(A) and erm(B). MICs of commonly used antibiotics as well as the presence of macrolide resistance determinant genes in all isolates were tested. Seventy one pneumococcal isolates collected at Institute for Medical Research (IMR) were included in this study. Phenotypic characterization, MIC determination using E-test strips and polymerase chain reactions for antibiotic resistance determination were included. Among the isolates, 25 (35.2%) isolates were erythromycin susceptible, 3 (4.2%) were intermediate and 42 (60.6%) were resistant. Fifty three isolates (74.7%) were found with mef(A) alone, 15 (21.1%) isolates with erm(B) + mef(A) combination and 3 (4.2%) isolates with none of the two genes. The in vitro activity of...
The Clinical Significance of Macrolide‐Resistant Streptococcus pneumoniae: It’s All Relative
Clinical Infectious Diseases, 2004
Macrolides are currently recommended as first-line agents for the empirical treatment of community-acquired pneumonia. Heavy use of these agents for a variety of indications has resulted in an increasing incidence of macrolide resistance among pneumococcal isolates. Although several case reports and small case series have suggested that in vitro macrolide resistance is associated with treatment failure in cases of pneumococcal pneumonia, other observational data suggest that drug susceptibility testing may not correlate with treatment failure. In this article, we review current information on the mechanisms of macrolide resistance and the pharmacodynamics of macrolide therapy, together with efficacy data from animal models and clinical observations, to begin to gauge the clinical significance of macrolide resistance in Streptococcus pneumoniae. Areas for further investigation are highlighted.
Antimicrobial Agents and Chemotherapy, 2003
pneumoniae Streptococcus Azithromycin against Efficacies of Clarithromycin and Influence of Macrolide Susceptibility on http://aac.asm.org/content/47/2/739 Updated information and services can be found at: These include: REFERENCES http://aac.asm.org/content/47/2/739#ref-list-1 at: This article cites 19 articles, 12 of which can be accessed free CONTENT ALERTS more» articles cite this article), Receive: RSS Feeds, eTOCs, free email alerts (when new http://journals.asm.org/site/misc/reprints.xhtml Information about commercial reprint orders: http://journals.asm.org/site/subscriptions/ To subscribe to to another ASM Journal go to: on December 4, 2013 by guest http://aac.asm.org/ Downloaded from on December 4, 2013 by guest http://aac.asm.org/
Mechanisms of Macrolide Resistance in Clinical Pneumococcal Isolates in France
Antimicrobial Agents and Chemotherapy, 2001
The genetic basis of macrolide resistance was investigated in a collection of 48 genotypically unrelated clinical isolates of Streptococcus pneumoniae obtained between 1987 and 1997 in France. All strains were resistant to erythromycin, clindamycin, and streptogramin B, exhibiting a macrolide-lincosamide-streptogramin B resistance phenotype, and harbored the erm(B) gene. None of the strains carried the mef(A) or erm(A) subclass erm(TR) gene.