Macrolide–lincosamide–streptogramin B resistance phenotypes and genotypes among Staphylococcus aureus clinical isolates in Japan

In total, 269 methicillin-resistant Staphylococcus aureus (MRSA) and 434 methicillin-susceptible S. aureus (MSSA) isolates were investigated to determine their macrolide-lincosamide-streptogramin B (MLS(B)) resistance phenotypes and genotypes. The constitutive phenotype (61.3% in MRSA, 1.3% in MSSA) and erm(A) gene predominated among the 261 erythromycin-resistant MRSA isolates, while the inducible phenotype (38.7% in MRSA, 94.0% in MSSA) and erm(C) gene were more prevalent among the 150 erythromycin-resistant MSSA isolates. There was a higher incidence of the MLS(B) inducible phenotype compared with other countries, perhaps because MLS(B) antibiotics are not recommended as first-line agents against S. aureus in Japan.     

Effect of ponsinomycin on cyclosporin pharmacokinetics

Summary The influence of treatment with ponsinomycin, a new macrolide antibiotic, on the pharmacokinetics of cyclosporin A has been studied in 10 renal transplant patients. The pharmacokinetics of cyclosporin A was investigated at steady state, before and during treatment with ponsinomycin.On average, the blood levels of cyclosporin A were doubled by the macrolide, possibly due to a decrease in elimination or/and to an increase in absorption.Ponsinomycin should be use very carefully in patients treated with cyclosporin A.     

Influence of macrolides on mucoid alginate biosynthetic enzyme from Pseudomonas aeruginosa

Objective: The long-term administration of erythromycin (EM), clarithromycin (CAM) or azithromycin (AZM) has generally resulted in a favorable outcome for patients with diffuse panbronchiolitis (DPB) infected with mucoid Pseudomonas aeruginosa. To elucidate the mechanism involved, the influence of macrolides on mucoid alginate production by P. aeruginosa was investigated in vitro.
Methods: The macrolides used in this study were EM with a 14-membered ring, AZM with a 15-membered ring, midecamycin (MDM) with a 16-membered ring, and CP-4305, which has had mycarose removed from MDM, The effects of macrolides on mucoid P. aeruginosa were investigated by quantitative assay of alginate production and inhibition of guanosine diphospho-D-mannose dehydrogenase activity.
Results: After incubation with EM, AZM and CP-4305, the structural material of P. aeruginosa biofilm was distorted, and the enzymatic activity of GDP-D-mannose dehydrogenase, the most important enzyme in mucoid alginate biosynthesis, was inhibited. However, these effects were not observed with the 16-membered macrolide MDM.
Conclusions: The basic mechanism of clinical efficacy seen characteristically in 14- or 15-membered macrolides for patients with airway biofilm disease depends on the ability of such macrolides to inhibit alginate production by P. aeruginosa. Furthermore, this suggests that the inhibitory effect observed with 14-, 15- and 16-membered macrolides may depend on the sugar chain connected with the macrolide ring.     

Characterisation of macrolide-non-susceptible Streptococcus pneumoniae colonising children attending day-care centres in Athens, Greece during 2000 and 2003

Nasopharyngeal Streptococcus pneumoniae isolates colonising young children are representative of isolates causing clinical disease. This study determined the frequency of macrolide-non-susceptible pneumococci, as well as their phenotypic and genotypic characteristics, among pneumococci collected during two cross-sectional surveillance studies of the nasopharynx of 2847 children attending day-care centres in the Athens metropolitan area during 2000 and 2003. In total, 227 macrolide-non-susceptible pneumococcal isolates were studied. Increases in macrolide non-susceptibility, from 23% to 30.3% (p <0.05), and in macrolide and penicillin co-resistance, from 3.4% to 48.6% (p <0.001), were identified during the study period. The M resistance phenotype, associated with the presence of the mef(A)/(E) gene, predominated in both surveys, and isolates carrying both mef(A)/(E) and erm(AM) were identified, for the first time in Greece, among the isolates from the 2003 survey. Pulsed-field gel electrophoresis analysis of the isolates from the 2000 survey indicated the spread of a macrolide- and penicillin-resistant clone among day-care centres. The serogroups identified most commonly in the study were 19F, 6A, 6B, 14 and 23F, suggesting that the theoretical protection of the seven-valent conjugate vaccine against macrolide-non-susceptible isolates was c. 85% during both study periods.     

肺炎链球菌对大环内酯类抗生素耐药机制研究

目的观察耐大环内酯类肺炎链球菌的耐药表型和基因型。方法用琼脂二倍稀释法测定耐大环内酯类肺炎链球菌对11种抗生素的最低抑菌浓度,耐药表型由红霉素和克林霉素双纸片法初步分型,通过PCR扩增耐药基因ermB和mefA进行基因分型,并测定ermB和mefA基因序列。结果　所有23株肺炎链球菌对大环内酯和克林霉素高度耐药,均表现为内在型耐药,没有发现诱导型耐药和M型耐药。ermB基因在23株肺炎链球菌中均检测到,其中5株同时检测到mefA基因,没有发现仅单一mefA基因阳性的菌株,基因型与耐药表型完全一致。所测ermB和mefA基因序列与基因库收录序列高度一致。 结论ermB基因介导的靶位改变可能是重庆地区肺炎链球菌对大环内酯类抗生素的主要耐药机制。     

Macrolide-Resistant Mycoplasma pneumoniae,United States

Macrolide-resistant Mycoplasma pneumoniae (MRMP) is highly prevalent in Asia and is now being reported from Europe. Few data on MRMP are available in the United States. Using genotypic and phenotypic methods, we detected high-level MRMP in 13.2% of 91 M. pneumoniae­–positive specimens from 6 US locations.     

Open clinical trial of rifabutin and clarithromycin therapy in Crohn''s disease

BACKGROUND: Crohn's disease, an inflammatory bowel disease in humans, has a suspected aetiology of Mycobacterium avium subsp. Paratuberculosis. AIMS: To evaluate the role of rifabutin and clarithromycin anti-Mycobacterium avium subsp. Paratuberculosis treatment in Crohn's disease patients using an open clinical trial. METHODS:. A total of 36 patients with acute presentations of Crohn's disease, whose sera tested positive against p35 and p36 antigens (two recombinant proteins of Mycobacterium avium subsp. Paratuberculosis), were selected for treatment with rifabutin and macrolide antibiotic therapy Rifabutin and macrolide antibiotic therapy medications included 250 mg 1 po bid clarithromycin and 150 mg 1 po bid Ri-fabutin accompanied with a probiotic. Crohn's disease patients' response to rifabutin and macrolide antibiotic therapy was monitored over a period ranging from 4 to 17 months. RESULTS: Seven patients (19.4%) withdrew from the study since they were unable to tolerate medications. Of the remaining 29 patients, 21 (58.3%) reached a sustained state of improvement, traditionally defined as a decrease of 70 points between their entrance and exit Crohn's disease activity index scores together with the absence of the need of all other Crohn's medications, such as immunosuppressants and corticosteroids. Three Crohn's disease patients [8. 3%) noticed significant improvements, but required other Crohn's medications, concurrently with rifabutin and macrolide antibiotic therapy, to achieve and sustain improvement. Only 5 Crohn's disease patients (13.8%) were non-responders, noticing no marked improvement while on rifabutin and macrolide antibiotic therapy. CONCLUSION: The data add further evidence to support the role of rifabutin and macrolide antibiotic therapy in the treatment of Crohn's disease specifically in those patients with evidence of Mycobacterium avium subsp. Paratuberculosis infection. A large multi-centre clinical trial is needed to further explore these findings.     

Macrolides attenuate mucus hypersecretion in rat airways through inactivation of NF-kappaB

Background and objective: To examine the effect of a 14‐membered ring macrolide on airway mucus hypersecretion in rats treated with LPS. Methods: Mucus hypersecretion in rat airways was induced by intratracheal instillation of LPS. Rats treated with or without LPS were administered roxithromycin (1–10 mg/kg), josamycin (10 mg/kg) or amoxicillin (40 mg/kg), orally for 4 days. Expression of Muc5ac, nuclear factor (NF)‐κB, and the mitogen‐activated protein (MAP) kinases p38 and ERK1/2 in bronchial epithelium were detected by RT‐PCR, immunohistochemistry or western blotting. Mucins, IL‐1β, IL‐8 and tumour necrosis factor (TNF)‐α in BAL fluid were assayed by enzyme‐linked lectin assay and ELISA. Results: LPS significantly induced the expression of Muc5ac mRNA and protein in bronchial epithelium, increased the release of mucins, IL‐1β, IL‐8 and TNF‐α, and increased neutrophil numbers in BAL. Moreover, LPS increased staining for NF ‐ κB in the cytoplasm as well as nuclear translocation of NF ‐ κB in airway epithelial cells. Upregulated expression of Muc5ac mRNA correlated positively with NF ‐ κB activation and the levels of cytokines (P < 0.05). Roxithromycin (5 and 10 mg/kg) significantly attenuated bronchial Muc5ac expression and NF ‐ κB nuclear translocation stimulated by LPS, and reduced neutrophil numbers, mucins and inflammatory cytokines in BAL (P < 0.05). However, LPS‐stimulated expression of p38 and ERK1/2 in airway epithelium was not affected by roxithromycin. Josamycin and amoxicillin had no effects on Muc5ac expression, NF ‐ κB activation or cytokine release. Conclusions: Roxithromycin inhibits the pulmonary inflammatory response and airway mucus hypersecretion induced by LPS. The inhibitory effect of roxithromycin on airway mucus hypersecretion may be mediated through reduction of NF ‐ κB activation, neutrophil infiltration and release of inflammatory cytokines in the lung.