The use of macrolides in treatment of upper respiratory tract infections

Antimicrobial resistance is a growing problem among upper respiratory tract pathogens. Resistance to β-lactam drugs among Streptococcus pneumoniae, Haemophilus influenzae, and Streptococcus pyogenes is increasing. As safe and well-tolerated antibiotics, macrolides play a key role in the treatment of community-acquired upper respiratory tract infections (RTIs). Their broad spectrum of activity against gram-positive cocci, such as S. pneumoniae and S. pyogenes, atypical pathogens, H. influenzae (azithromycin and clarithromycin), and Moraxella catarrhalis, has led to the widespread use of macrolides for empiric treatment of upper RTIs and as alternatives for patients allergic to β-lactams. Macrolide resistance is increasing among pneumococci and recently among S. pyogenes, and is associated with increasing use of the newer macrolides, such as azithromycin. Ribosomal target modification mediated by erm(A) [erm(TR)] and erm(B) genes and active efflux due to mef(A) and mef(E) are the principal mechanisms of resistance in both S. pneumoniae and S. pyogenes. Recently, ribosomal protein and RNA mutations have been found to be responsible for acquired resistance to macrolides in S. pneumoniae, S. pyogenes, and H. influenzae. Although macrolides are only weakly active against macrolide-resistant streptococci species, producing an efflux pump (mef), and are inactive against pathogens with ribosomal target modification (erm), treatment failures are uncommon. Therefore, macrolide therapy, for now, remains a good alternative for treatment of upper RTIs; however, continuous monitoring of the local resistance patterns is essential.     

Ribosomal resistance: Emerging problems and potential solutions

Many systemic antibiotics use ribosomal inhibition to suppress the replication of bacteria. Current research suggests that resistance to macrolide, lincosamide, and streptogramin B (MLS_B) antibiotics is emerging among clinical isolates of Streptococcus pyogenes and Streptococcus pneumoniae. Erythromycin methylases, encoded by erm genes, modify an essential adenine residue in 23S rRNA and confer cross-resistance to MLS_B antibiotics. More recently, macrolide efflux (mef) genes were identified in isolates of S. pyogenes and S. pneumoniae that show resistance to 14- and 15-membered macrolides (M phenotype). Resistance to MLSB has been associated with the increased use of erythromycin, and the recent emergence of the M phenotype has coincided with the marketing of newer macrolides. However, despite increasing macrolide resistance among clinical isolates of S. pneumoniae, convincing data on treatment failures directly attributable to MLSB or M phenotypes are limited. Possible solutions to emerging MLS_B and M phenotype resistance include the introduction of alternative antibiotics, the more prudent use of antibiotics, combination therapy, molecular diagnostics, enhanced understanding of pharmacodynamic variables, and redefined resistance breakpoints.     

The use of ketolides in treatment of upper respiratory tract infections

Recent surveillance studies suggest that the incidence of resistance to macrolide antibiotics in common communityacquired respiratory tract pathogens, particularly Streptococcus pneumoniae and Streptococcus pyogenes, is increasing and limiting the usefulness of these drugs. The ketolides, of which telithromycin is the first to be available for clinical use (but not yet in the United States), represent a new class of antibacterials developed specifically to combat respiratory tract pathogens that have acquired resistance to macrolides. The ketolides possess innovative structural modifications, a 3-keto group and a large N-substituted C11, C12-carbamate side chain. This novel structure allows ketolides, which are inhibitors of protein synthesis, to exert a more effective interaction with domain II of the 23S rRNA, enhancing binding to bacterial ribosomes and allowing binding to macrolide-lincosamidestreptogramin B-resistant ribosomes. This novel chemical structure also promotes greater stability of telithromycin in acid conditions, providing the potential for greater stability in gastric fluid and at cellular/tissue levels. Early clinical trials support the bacteriologic and clinical efficacy of telithromycin in the treatment of upper respiratory tract infections (RTIs) such as streptococcal pharyngitis and acute sinusitis, including infections caused by macrolide-resistant S. pneumoniae and S. pyogenes. Common adverse side effects associated with telithromycin are predominantly gastrointestinal, usually of mild to moderate severity, and rarely involve withdrawal of the drug. Telithromycin represents an attractive option for the empiric treatment of upper RTIs, especially as resistance to macrolides is likely to continue to increase.     

Carrier state of Haemophilus influenzae type b (Hib), Streptococcus pneumoniae,Streptococcus pyogenes,Neisseria meningitidis and Corynebacterium diphtheriae among school children in Pokhara,Nepal

ObjectiveTo determine the incidence of carrier state of Haemophilus influenzae type b, Streptococcus pneumoniae (S. pneumoniae), Streptococcus pyogenes, Neisseria meningitidis and Corynebacterium diphtheriae among school children.MethodsSpecimen from posterior pharyngeal wall and tonsils were collected on calcium alginate coated swabs from 102 participants. Processing of specimen and antimicrobial susceptibility testing was done by standard procedures.ResultsPotential pathogens isolated in our study were S. pneumoniae (14.7%), Staphylococcus aureus (12.7%), Corynebacterium diphtheriae (3.9%), Streptococcus pyogenes (3.9%) and Haemophilus influenzae (1.9%). Important findings in antibiogram include high resistance of S. pneumoniae to penicillin (73%) and resistance of Staphylococcus aureus to oxacillin (23%).ConclusionsPharyngeal colonization by S. pneumoniae among school children was found high and there is need of introduction of pneumococcal vaccines among children. Despite expected universal vaccination, pharyngeal colonization by Corynebacterium diphtheriae is possible and there is possibility of transmission.     

What is the clinical impact of macrolide resistance?

Respiratory tract infections are treated empirically. Treatment is based on the likely pathogens and their antibiotic susceptibility. The most common respiratory tract pathogen is Streptococcus pneumoniae. In the United States, approximately 25% to 30% of S. pneumoniae are resistant to erythromycin and other macrolides. There are two mechanisms of resistance: ribosomal methylation that causes high-level resistance, and an efflux pump that causes low-level resistance. Macrolides are ineffective in animal models that use pneumococcal isolates with the methylase- or efflux-mediated resistance mechanisms. There are many case reports that describe clinical failure and isolation of a macrolide-resistant pneumococcus while a patient receives macrolide treatment. Two recent studies that included macrolide-susceptible and macrolideresistant pneumococci showed that breakthrough bacteremia in patients receiving macrolide treatment occurred only with macrolide-resistant isolates. Study of bacteremic disease ensures the pathogenic role of the pneumococcus; however, it underestimates the true clinical impact of macrolide resistance.     

Current issues in the management of bacterial respiratory tract disease: the challenge of antibacterial resistance

The worldwide burden of respiratory tract disease is enormous. Resistance to penicillins, macrolides, and cephalosporins is now detected among the leading bacterial pathogens that cause respiratory tract infections (RTIs)-Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. The increasing role of atypical/intracellular pathogens (eg, Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella pneumophila) in RTIs, as well as their increase in antibiotic resistance prevalence, continues to be of great concern. More recently introduced treatment options for RTIs include the newer respiratory fluoroquinolones, along with the macrolides and azalides. Although these agents demonstrate good activity against common respiratory pathogens, reduced susceptibility to these agents has been reported. The ketolides are recently developed antibacterial agents with targeted-spectrum activity against common respiratory tract pathogens, including atypical/intracellular pathogens, and a low potential for inducing resistance. These promising new drugs have shown in vitro and in vivo efficacy in the treatment of community-acquired RTIs, such as community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute bacterial maxillary sinusitis.     

Correlation between usage of macrolide antibiotic and resistance of Streptococcus pneumoniae clinic isolates from chongqing children's hospital

To investigate the reasons of growing resistance problem of Streptococcus pneumoniae against macrolide in Chongqing, a retrospective method was employed to measure the minimal inhibition concentrations (MIC) of macrolide antibiotic against 1,210 S. pneumoniae clinic isolates. The defined daily doses (DDDs) of macrolide antibiotic were calculated. Polymerase chain reaction (PCR) was used to determine the presence of the erythromycin‐resistant genes in 100 macrolide‐resistant S. pneumoniae isolates. A decrease in macrolide consumption, from 371,100 DDDs in 2002 to 182,500 DDDs in 2005 (51% reduction); however, the rate of erythromycin resistance in S. pneumoniae showed continued increase from 88.0% in 2002 to 96.0% in 2005. No linear correlation was observed between the decline in macrolide consumption and continued increase in resistant rate in S. pneumoniae. In 100 macrolide‐resistant S. pneumoniae isolates, 68 had both erm(B) and mef(A) genotypes, 10 only had the erm(B), 20 only had the mef(A). Co‐existences of ribosomal modification coded by erm(B) gene and efflux effects coded by mef(A) gene were the main resistance mechanism against macrolides and might be attributed to the high drug resistance of S. pneumoniae in Chongqing. Pediatr Pulmonol. 2009; 44:917–921. © 2009 Wiley‐Liss, Inc.     

Susceptibility of bacterial isolates from community-acquired infections in sub-Saharan Africa and Asia to macrolide antibiotics

Objective To review the literature on the susceptibility of common community pathogens in sub‐Saharan Africa and Asia to the macrolide antibiotics. Methods Inclusion criteria required that isolates were collected since 2004 to ensure results were of contemporary relevance. The data were aggregated by region, age group and sterility of site of culture sample. Results A total of 51 studies were identified, which reported the macrolide antimicrobial susceptibilities of common bacterial pathogens isolated since 2004. In general, there was less macrolide resistance in African than in Asian isolates. Most African studies reported high levels of macrolide susceptibility in Streptococcus pneumoniae, whereas most Chinese studies reported high levels of resistance. There was very little information available for Gram‐negative organisms. Conclusions Susceptibility of the pneumococcus to macrolides in SSA remains high in many areas, and good activity of azithromycin has been shown against Salmonellae spp. in Asia. In urban areas where high antibiotic consumption is prevalent, there was evidence of increased resistance to macrolides. However, there is no information on susceptibility from large areas in both continents.     

Bacteria and viruses that cause respiratory tract infections during the pilgrimage (Haj) season in Makkah,Saudi Arabia

objective To determine the incidence and type of RTI-causing bacteria and viruses during a period of epidemic infections. method A total of 395 sputum specimens and 761 throat swabs were collected during the 1991 and 1992 pilgrimage seasons (Haj to Makkah Al-Mukarama, Saudi Arabia) from patients referred to one hospital and three dispensaries with symptoms of respiratory tract infections. All 761 throat swabs of both Haj seasons were also screened for the presence of viral pathogens with monoclonal antibodies specific for 7 viruses known to cause respiratory infections. results Bacterial pathogens were detected in 118 (29.9%) specimens. During the 1991 Haj season Haemophilus influenzae was the most frequent bacterial pathogen detected (10%), followed by Klebsiella pneumoniae (5.2%), Streptococcus pneumoniae (4.8%), Staphylococcus aureus (3.8%) and Streptococcus pyogenes (2.4%). In the 1992 Haj season Klebsiella pneumoniae was predominant (15.1%), followed by Haemophilus influenzae and Streptococcus pneumoniae (12.3%). Screening of all sputum specimens for acid-fast bacteria showed that the overall incidence rate of tuberculosis was 1%. Cultures from the 761 throat swabs were largely negative for bacteria except for Streptococcus pyogenes isolated from 7 patients. Viruses were detected in 148 (19.5%) specimens with influenza A and adenovirus being the most common viruses. conclusion The pattern of virus prevalence in the 1991 and 1992 pilgrimage seasons was identical: influenza A and adenovirus predominated. Thus these two viruses should be targeted in future prophylactic measures.     

Invasive bacterial infections following influenza: a time-series analysis in Montréal, Canada, 1996-2008

Please cite this paper as: Allard et al. (2012) Invasive bacterial infections following influenza: a time‐series analysis in Montréal, Canada, 1996–2008. Influenza and Other Respiratory Viruses 6(4), 268–275. Background Shared seasonal patterns, such as between influenza and some respiratory bacterial infections, can create associations between phenomena not causally related. Objectives To estimate the association of influenza with subsequent bacterial infections after full adjustment for confounding by seasonal and long‐term trends. Methods Time series of weekly counts of notified cases of invasive infections with Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae and Streptococcus pyogenes, in Montréal, Canada, 1996–2008, were modelled by negative binomial regression, with terms representing seasonal and long‐term trends and terms for numbers of positive laboratory tests for influenza A and B. Results The associations of S. pneumoniae, H. influenzae and N. meningitidis with influenza disappeared after seasonal terms were added to the model. However, the influenza B count remained associated with the S. pyogenes counts for the same week and the following week: S. pyogenes incidence rate ratios were 1.0376 (95% CI: 1.0009–1.0757) and 1.0354 (0.9958–1.0766), respectively, for each increase of 1 in the influenza count. Conclusions Influenza B accounts for about 8percnt; of the incidence of invasive S. pyogenes infections, over and above any effect associated with modellable seasonal and long‐term trends. This association of influenza B with S. pyogenes infections can be attributed largely to the years 1997, 2001, 2007 and 2008, when late peaks in influenza B counts were followed by peaks in S. pyogenes notifications. This finding reinforces the case for universal immunization against influenza, as partial protection against the ‘flesh eating disease’.     

Epidemiology and antibiotic resistance of bacterial meningitis in Dapaong,northern Togo

ObjectiveTo assess the seasonality of the bacterial meningitis and the antibiotic resistance of incriminated bacteria over the last three years in the northern Togo.MethodsFrom January 2007 to January 2010, 533 cerebrospinal fluids (CSF) samples were collected from patients suspected of meningitis in the Regional Hospital of Dapaong (northern Togo). After microscopic examination, samples were cultured for bacterial identification and antibiotic susceptibility.ResultsThe study included 533 patients (306 male and 227 female) aged from 1 day to 55 years [average age (13.00±2.07) years]. Bacterial isolation and identification were attempted for 254/533 (47.65%) samples. The bacterial species identified were: Neisseria meningitidis A (N. meningitidis A) (58.27%), Neisseria meningitidis W135 (N. meningitidis W135) (7.09%), Streptococcus pneumoniae (S. pneumoniae) (26.77%), Haemophilus influenza B (H. influenza B) (6.30%) and Enterobacteriaceae (1.57%). The results indicated that bacterial meningitis occur from November to May with a peak in February for H. influenzae and S. pneumoniae and March for Neisseriaceae. The distribution of positive CSF with regards to the age showed that subjects between 6 and 12 years followed by subjects of 0 to 5 years were most affected with respective frequencies of 67.82% and 56.52% (P<0.001). Susceptibility tests revealed that bacteria have developed resistance to several antibiotics including aminosides (resistance rate >20% for both bacterial strains), macrolides (resistance rate > 30% for H. influenzae) quinolones (resistance rate >15% for H. influenzae and N. meningitidis W135). Over three years, the prevalence of S. pneumoniae significantly increased from 8.48% to 73.33% (P<0.001), while the changes in the prevalence of H. influenzae B were not statistically significant: 4.24%, vs. 8.89%, (P = 0.233).ConclusionsOur results indicate that data in African countries differ depending on geographical location in relation to the African meningitis belt. This underlines the importance of epidemiological surveillance of bacterial meningitis.     

Distribution of erm genes and low prevalence of inducible resistance to clindamycin among staphylococci isolates

IntroductionResistance to macrolides, lincosamides and streptogramins B (MLS_B antibiotics) in staphylococci may be due to modification in ribosomal target methylase encoded by erm genes. The expression of MLS_B resistance lead to three phenotypes, namely constitutive resistance (cMLS_B), inducible resistance (iMLS_B), and resistance only to macrolides and streptogramins B (MS_B). The iMLS_B resistance is the most difficult to detect in the clinical laboratory.ObjectiveThis study investigated the expression of MLS_B resistance and the prevalence of the erm genes among 152 clinical isolates of Staphylococcus aureus and coagulase-negative Staphylococcus (CNS) from Hospital de Clínicas de Porto Alegre.MethodsPrimary MLS_B resistance was detected by the disk diffusion method. Isolates with iMLS_B phenotype were tested by double-disk induction method. All isolates were tested by a genotypic assay, PCR with specific primers.ResultsA total of 46.7% of staphylococci were positive for cMLS_B; 3.3% for iMLS_B and 3.3% for MS_B. One or more erm genes were present in 50.1% of isolates. The gene ermA was detected in 49 isolates, ermC in 29 and ermB in 3.ConclusionThe prevalence of the ermA, ermB and ermC genes were 29.6%, 17.1% and 0.66% respectively, and constitutive resistance was the most frequent as compared to the other two phenotypes.     

The Impact of Vaccination on Rhinosinusitis and Otitis Media

Routine childhood vaccination has affected frequency and bacteriology of acute otitis media (AOM) and acute bacterial rhinosinusitis (ABRS). Routine influenza vaccination moderately reduces AOM, and the Haemophilus influenzae type b vaccine likely had a minor role in AOM and ABRS. The conjugated pneumococcal vaccine has drastically reduced invasive pneumococcal disease and caused a moderate decrease in AOM and, likely, ABRS. The vaccine serotypes of Streptococcus pneumoniae have been all but eliminated, but other serotypes have emerged as potential causes of invasive disease. Antibiotic resistance in pneumococcal disease seems to have decreased. A decrease in the overall prevalence of S. pneumoniae may have resulted in an increased incidence of Staphylococcus aureus as a pathogen in AOM and ABRS due to the concept of bacterial interference.     

Changing epidemiology of bacterial meningitis

Immunization against the most common meningeal pathogens is the leading factor associated with decreased incidence of bacterial meningitis in countries where routine vaccination is available. This is most dramatically illustrated by the reduction in the incidence of Haemophilus influenzae type b meningitis. The incidence of bacterial meningitis has decreased by 55% since the introduction of the H. influenzae type b conjugate vaccine in 1990. H. influenzae occurred primarily in children younger than 5 years of age, and so the median age of patients with bacterial meningitis has now increased to 39 years of age in the United States, and the leading pathogen is currently Streptococcus pneumoniae. Three other control measures (ie, universal screening and antibiotic prophylaxis of pregnant women for Group B streptococci and the implementation and availability of the S. pneumoniae and Neisseria meningitidis conjugate vaccines) have likely further decreased the incidence of these meningeal pathogens. Lastly, the worldwide emergence of multidrug-resistant pneumococci has complicated the empiric therapy of bacterial meningitis.     

Achieving bacterial eradication using pharmacokinetic/ pharmacodynamic principles

Evidence from studies in otitis media indicates that antimicrobials and dosing regimens that have equivalent bacteriologic efficacy against susceptible pathogens can have significantly different bacteriologic success rates against resistant strains of the same species. Unlike macrolide and fluoroquinolone resistance, penicillin resistance can be overcome in Streptococcus pneumoniae by increasing the dose, and hence increasing the time for which the serum concentrations are above the MIC. The new clinical formulation of extra-strength amoxicillin-clavulanate provides 90 mg/kg per day amoxicillin plus 6.4 mg/kg per day clavulanate (14:1) divided every 12 h, compared with 45/6.4 mg/kg per day b.i.d. with conventional dosing. The pharmacokinetic/pharmacodynamic (PK/PD) profiles of extra-strength amoxicillin-clavulanate predict that the new formulation will be more effective than the conventional formulation against S. pneumoniae with elevated amoxicillin MICs and against Haemophilus influenzae. In an open-label, non-comparative study in children with acute otitis media, the extra-strength formulation had high bacteriologic success rates against the major respiratory pathogens, including penicillin-resistant S. pneumoniae. The development of new antimicrobial agents and formulations should be aimed at meeting PK/PD parameters predictive of bacterial eradication of both susceptible and resistant strains.     

突变敏感性分子开关检测肺炎支原体对大环内酯类抗生素的耐药性研究

目的 应用突变敏感性分子开关检测肺炎支原体对大环内酯类抗生素的耐药性。方法 采用微量稀释法检测5种常用大环内酯类抗生素对40株Mp临床分离株的药物敏感性;建立高保真聚合酶和3'硫化修饰引物的分子开关,用分子开关进行Mp临床分离株的PCR扩增,检测其是否存在Mp 23S rRNA 2063、2064和2617 3个热点突变,并通过基因测序进一步确定是否存在点突变,分析点突变与大环内酯类抗生素敏感性之间的关系。结果 5种大环内酯类抗生素中,Mp对14元环的红霉素和克拉霉素耐药程度最高,其MIC≥128 mg/L;对15元环的大环内酯类抗生素阿奇霉素和交沙霉素相对敏感,其中交沙霉素抗Mp活性最高,其MIC≤4 mg/L。用高保真聚合酶和3'硫化修饰引物的分子开关行PCR扩增,检测出35株发生了2063位点基因突变,3株发生2064位点基因突变,未检测出2617位点突变。用基因测序检测到35株Mp发生A2063G的突变,3株发生A2064G的突变,未检测到2617位点突变,与分子开关的检测结果一致,并且2063、2064位点突变Mp株均对大环内酯类药物高度耐药。结论 分子开关可识别23S rRNA基因突变,可用于分析Mp对大环内酯类抗生素的敏感性。     

Ceforanide (BL-S 786) in the treatment of community-acquired bacterial pneumonia

Summary Ceforanide (BL-S 786) is a new long-acting parenteral cephalosporin which has the major pharmacologic advantage of requiring only twice a day dosage. We treated 28 adult patients with community-acquired bacterial pneumonia using doses of 500 or 1000 mg every 12 hours. Twenty-four of 28 infections were due toStreptococcus pneumoniae and/orHemophilus influenzae, and all pathogens were susceptible in vitro to both cephalothin and ceforanide. Patients were treated for a mean of 7.5 days, and all showed a good clinical and radiographic response with no mortality. Of the 13 patients withH. influenzae, the organism could still be recovered during therapy in 9/12 and post therapy in 3/8. One clinical superinfection (sepsis due toPseudomonas aeruginosa) occurred during therapy. Side effects with therapy included thrombocytosis (15), asymptomatic eosinophilia (5), and mild elevation of the serum transaminases (3). These studies suggest that ceforanide is a safe and effective agent for the treatment of adult patients with bacterial pneumonia due toS. pneumoniae; further experience in therapy ofH. influenzae is needed because of frequent failure of ceforanide to eradicate this organism from the sputum.

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Ceforanid (BL-S 786) in der Behandlung der nicht im Krankenhaus erworbenen bakteriellen Pneumonie

Zusammenfassung Ceforanid (BL-S 786) ist ein neues, lang wirkendes parenterales Cefalosporin, das den wesentlichen pharmakologischen Vorteil hat, daß es nur zweimal am Tag verabreicht werden muß. Wir behandelten 28 erwachsene Patienten mit nicht im Krankenhaus erworbener bakterieller Pneumonie, dabei wurden Dosen von 500 mg oder 1000 mg alle 12 Stunden gegeben. Vierundzwanzig der 28 Infektionen waren durchStreptococcus pneumoniae und/oderHaemophilus influenzae verursacht, und alle pathogenen Erreger waren in vitro empfindlich gegenüber Cefalothin und Ceforanid. Die Kranken wurden im Durchschnitt 7,5 Tage lang behandelt, alle zeigten einen guten klinischen und röntgenologischen Therapieerfolg, keiner verstarb. Von den 13 Patienten mitHaemophilus influenzae konnte der Organismus während der Therapie noch bei 9/12 und nach Abschluß der Therapie noch bei 3/8 gefunden werden. Unter der Behandlung kam es in einem Fall zu einer klinischen Superinfektion (Sepsis durchPseudomonas aeruginosa). Nebenwirkungen der Therapie umfaßten Thrombozytose (15), asymptomatische Eosinophilie (5) und leichte Erhöhung der Serum-Transaminasen (3). Die vorgelegten Untersuchungen lassen annehmen, daß Ceforanid ein sicheres und wirksames Mittel für die Behandlung erwachsener Patienten mit bakterieller Pneumonie durchS. pneumoniae ist; in der Behandlung vonH. influenzae bedarf es noch weiterer Erfahrung, da es unter Ceforanid häufig nicht gelungen ist, diesen Erreger aus dem Sputum zu beseitigen.

     

Clinical efficacy of macrolide antibiotics against genetically determined macrolide-resistant Mycoplasma pneumoniae pneumonia in paediatric patients

Background and objective: Since 2000, the prevalence of macrolide‐resistant (MR) Mycoplasma pneumoniae has increased among paediatric patients in Japan. To determine the efficacy of macrolides against MR M. pneumoniae pneumonia, microbiological and clinical efficacies were compared during the antibiotic treatment. Methods: Samples from a total of 30 children with M. pneumoniae pneumonia, as confirmed by PCR and serology, were analyzed. Primers for domain V of 23S rRNA were used, and DNA sequences of the PCR products were compared with the sequence of an M. pneumoniae reference strain. Results: Isolates from 21 patients demonstrated point mutations, and these patients were defined as MR. The remaining nine patients, whose isolates showed no point mutations, were categorized as control (macrolide‐sensitive) patients. The number of M. pneumoniae in nasopharyngeal samples from the control group decreased rapidly 48 h after initiation of macrolide treatment and showed a close relationship with clinical outcome. In contrast, the number of M. pneumoniae 48 h after initiation of macrolide treatment were significantly higher in samples from MR patients than in samples from macrolide‐sensitive patients. In 15 of 21 MR patients, fever persisted for more than 48 h after the initiation of macrolide treatment. When treatment was changed to minocycline, fever disappeared within 48 h in all these MR patients. There were no differences between MR patients who demonstrated a reduction in fever and those in whom fever persisted after 48 h of macrolide treatment. Conclusions: The microbiological and clinical efficacies of macrolides for treating patients with MR M. pneumoniae pneumonia were low. These results show that macrolides are clearly less effective in patients with MR M. pneumoniae pneumonia.     

Azithromycin: Single 1.5g dose in the treatment of patients with atypical pneumonia syndrome—A randomized study

Summary An open comparative study was undertaken in order to assess the efficacy and safety of a single dose of azithromycin in the treatment of community-acquired atypical pneumonia. A total of 100 adult patients with atypical penumonia syndrome were randomized to receive 1.5 g of azithromycin as a single dose, or 500 mg once daily for 3 days. The presence ofMycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia psittaci, Coxiella burnetii, andLegionella pneumophila infection was diagnosed by serological tests. Control clinical examinations were performed 72h, 10–12 days and 4 weeks after treatment initiation. Among 96 patients (48 in each group) who were evaluable for clinical efficacyM. pneumoniae infection was confirmed in 24,C. pneumoniae in nine,C. psittaci in five,C. burnetii in six, andL. pneumophila in five. Forty-seven patients (97.9%) in each group were cured. Side effects were observed in two patients in the single-dose group, and one patient in the 3-day group. In conclusion, a single 1.5 g dose of azithromycin may be an alternative to the standard 3-day azithromycin regimen in the treatment of outpatients with atypical pneumonia syndrome.     

Antimicrobial activity of innate immune molecules against <Emphasis Type="Italic">Streptococcus pneumoniae,Moraxella catarrhalis</Emphasis> and nontypeable <Emphasis Type="Italic">Haemophilus influenzae</Emphasis>

Background  

Despite its direct connection to the nasopharynx which harbors otitis media pathogens as part of its normal flora, the middle ear cavity is kept free of these bacteria by as yet unknown mechanisms. Respiratory mucosal epithelia, including those of the middle ear and eustachian tube, secrete antimicrobial effectors including lysozyme, lactoferrin and β defensins-1 and -2. To elucidate the role of these innate immune molecules in the normal defense and maintenance of sterility of respiratory mucosa such as that of the middle ear, we assessed their effect on the respiratory pathogens nontypeable Haemophilus influenzae (NTHi) 12, Moraxella catarrhalis 035E, and Streptococcus pneumoniae 3, and 6B.